摘要
瘦素是肥胖（ob）基因的脂肪细胞源性激素产物。瘦蛋白在免疫功能的维持和体内平衡中作为免疫调节因子起着重要的调节作用。实际上，近年来，瘦素作为免疫调节剂在炎症和免疫应答中的作用已引起越来越多的关注。瘦素主要通过调节单核细胞，树突状细胞，嗜中性粒细胞，NK细胞和树突状细胞的免疫调节来影响应答，此外还调节T和B细胞的发育和功能。瘦素也是重要的炎症调节剂，其中高表达影响IL-6，C反应蛋白和TNF-α的分泌率。此外，瘦素高度参与与人类代谢，炎性反应，细胞发育和疾病（包括造血）有关的过程。由于其多样化的免疫相关功能，瘦素已被开发为治疗自身免疫性疾病的潜在治疗靶标。
关键词: 瘦素，免疫应答，自身免疫性疾病，脂肪细胞来源的，肥胖（ob）基因，树突状细胞。
图形摘要
[1]
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425-32.
[http://dx.doi.org/10.1038/372425a0] [PMID: 7984236]
[http://dx.doi.org/10.1038/372425a0] [PMID: 7984236]
[2]
Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006; 443(7109): 289-95.
[http://dx.doi.org/10.1038/nature05026] [PMID: 16988703]
[http://dx.doi.org/10.1038/nature05026] [PMID: 16988703]
[3]
Alavi K, Schwartz MZ, Prasad R, O’connor D, Funanage V. Leptin: a new growth factor for the small intestine. J Pediatr Surg 2002; 37(3): 327-30.
[http://dx.doi.org/10.1053/jpsu.2002.30805] [PMID: 11877642]
[http://dx.doi.org/10.1053/jpsu.2002.30805] [PMID: 11877642]
[4]
Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1(11): 1155-61.
[http://dx.doi.org/10.1038/nm1195-1155] [PMID: 7584987]
[http://dx.doi.org/10.1038/nm1195-1155] [PMID: 7584987]
[5]
Iikuni N, Lam QLK, Lu L, Matarese G, La Cava A. Leptin and Inflammation. Curr Immunol Rev 2008; 4(2): 70-9.
[http://dx.doi.org/10.2174/157339508784325046] [PMID: 20198122]
[http://dx.doi.org/10.2174/157339508784325046] [PMID: 20198122]
[6]
Zavalza-Gómez AB, Anaya-Prado R, Rincón-Sánchez AR, Mora-Martínez JM. Adipokines and insulin resistance during pregnancy. Diabetes Res Clin Pract 2008; 80(1): 8-15. [J]
[http://dx.doi.org/10.1016/j.diabres.2007.12.012] [PMID: 18291552]
[http://dx.doi.org/10.1016/j.diabres.2007.12.012] [PMID: 18291552]
[7]
Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000; 62(3): 413-37. [J]
[http://dx.doi.org/10.1146/annurev.physiol.62.1.413] [PMID: 10845097]
[http://dx.doi.org/10.1146/annurev.physiol.62.1.413] [PMID: 10845097]
[8]
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998; 394(6696): 897-901. [J]
[http://dx.doi.org/10.1038/29795] [PMID: 9732873]
[http://dx.doi.org/10.1038/29795] [PMID: 9732873]
[9]
Howard JK, Lord GM, Matarese G, et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 1999; 104(8): 1051-9.
[http://dx.doi.org/10.1172/JCI6762] [PMID: 10525043]
[http://dx.doi.org/10.1172/JCI6762] [PMID: 10525043]
[10]
Gaucher EA, Miyamoto MM, Benner SA. Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein. Genetics 2003; 163(4): 1549-53.
[PMID: 12702697]
[PMID: 12702697]
[11]
Baumann H, Morella KK, White DW, et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 1996; 93(16): 8374-8.
[http://dx.doi.org/10.1073/pnas.93.16.8374] [PMID: 8710878]
[http://dx.doi.org/10.1073/pnas.93.16.8374] [PMID: 8710878]
[12]
Gualillo O, Eiras S, Lago F, Diéguez C, Casanueva FF. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci 2000; 67(20): 2433-41.
[http://dx.doi.org/10.1016/S0024-3205(00)00827-4] [PMID: 11065166]
[http://dx.doi.org/10.1016/S0024-3205(00)00827-4] [PMID: 11065166]
[13]
Matarese G. Leptin and the immune system: how nutritional status influences the immune response. Eur Cytokine Netw 2000; 11(1): 7-14.
[PMID: 10705294]
[PMID: 10705294]
[14]
Chua S C, Koutras I K, Han L, et al. Fine structure of the murine
leptin receptor gene: Splice site suppression is required to form two
alternatively spliced transcripts. Genomics 1997; 45(2): 0-270.
[15]
Devos R, Guisez Y, Van der Heyden J, et al. Ligand-independent dimerization of the extracellular domain of the leptin receptor and determination of the stoichiometry of leptin binding. J Biol Chem 1997; 272(29): 18304-10.
[http://dx.doi.org/10.1074/jbc.272.29.18304] [PMID: 9218470]
[http://dx.doi.org/10.1074/jbc.272.29.18304] [PMID: 9218470]
[16]
Tsiotra PC, Pappa V, Raptis SA, Tsigos C. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin’s actions. Metabolism 2000; 49(12): 1537-41.
[http://dx.doi.org/10.1053/meta.2000.18519] [PMID: 11145113]
[http://dx.doi.org/10.1053/meta.2000.18519] [PMID: 11145113]
[17]
Alexander WS, Starr R, Metcalf D, et al. Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction. J Leukoc Biol 1999; 66(4): 588-92.
[http://dx.doi.org/10.1002/jlb.66.4.588] [PMID: 10534114]
[http://dx.doi.org/10.1002/jlb.66.4.588] [PMID: 10534114]
[18]
Knobelspies H, Zeidler J, Hekerman P, Bamberg-Lemper S, Becker W. Mechanism of attenuation of leptin signaling under chronic ligand stimulation. BMC Biochem 2010; 11(1): 2.
[http://dx.doi.org/10.1186/1471-2091-11-2] [PMID: 20059770]
[http://dx.doi.org/10.1186/1471-2091-11-2] [PMID: 20059770]
[19]
Baumann H, Morella KK, White DW, et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 1996; 93(16): 8374-8.
[http://dx.doi.org/10.1073/pnas.93.16.8374] [PMID: 8710878]
[http://dx.doi.org/10.1073/pnas.93.16.8374] [PMID: 8710878]
[20]
Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83(7): 1263-71.
[http://dx.doi.org/10.1016/0092-8674(95)90151-5] [PMID: 8548812]
[http://dx.doi.org/10.1016/0092-8674(95)90151-5] [PMID: 8548812]
[21]
Guan XM, Hess JF, Yu H, Hey PJ, van der Ploeg LH. Differential expression of mRNA for leptin receptor isoforms in the rat brain. Mol Cell Endocrinol 1997; 133(1): 1-7.
[http://dx.doi.org/10.1016/S0303-7207(97)00138-X] [PMID: 9359467]
[http://dx.doi.org/10.1016/S0303-7207(97)00138-X] [PMID: 9359467]
[22]
Takaya K, Ogawa Y, Isse N, et al. Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats. Biochem Biophys Res Commun 1996; 225(1): 75-83.
[http://dx.doi.org/10.1006/bbrc.1996.1133] [PMID: 8769097]
[http://dx.doi.org/10.1006/bbrc.1996.1133] [PMID: 8769097]
[23]
Sweeney G. Leptin signalling. Cell Signal 2002; 14(8): 655-63.
[http://dx.doi.org/10.1016/S0898-6568(02)00006-2] [PMID: 12020765]
[http://dx.doi.org/10.1016/S0898-6568(02)00006-2] [PMID: 12020765]
[24]
Belouzard S, Rouillé Y. Ubiquitylation of leptin receptor OB-Ra regulates its clathrin-mediated endocytosis. EMBO J 2006; 25(5): 932-42.
[http://dx.doi.org/10.1038/sj.emboj.7600989] [PMID: 16482222]
[http://dx.doi.org/10.1038/sj.emboj.7600989] [PMID: 16482222]
[25]
Faggioni R, Feingold KR, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 2001; 15(14): 2565-71.
[http://dx.doi.org/10.1096/fj.01-0431rev] [PMID: 11726531]
[http://dx.doi.org/10.1096/fj.01-0431rev] [PMID: 11726531]
[26]
Arend WP. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 2002; 13(4-5): 323-40.
[http://dx.doi.org/10.1016/S1359-6101(02)00020-5] [PMID: 12220547]
[http://dx.doi.org/10.1016/S1359-6101(02)00020-5] [PMID: 12220547]
[27]
Spulber S, Bartfai T, Schultzberg M. IL-1/IL-1ra balance in the
brain revisited–Evidence from transgenic mouse models. Brain Behavior
& Immunity 2009; 32(5): 0-579.
[28]
Palin K, Verrier D, Tridon V, et al. Influence of the course of brain inflammation on the endogenous IL-1beta/IL-1Ra balance in the model of brain delayed-type hypersensitivity response to bacillus Calmette-Guérin in Lewis rats. J Neuroimmunol 2004; 149(1-2): 22-30.
[http://dx.doi.org/10.1016/j.jneuroim.2003.12.005] [PMID: 15020061]
[http://dx.doi.org/10.1016/j.jneuroim.2003.12.005] [PMID: 15020061]
[29]
Dayer J-M. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology 2003; 42(90002): 3ii-10.
[30]
Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol 2005; 174(11): 6820-8.
[http://dx.doi.org/10.4049/jimmunol.174.11.6820] [PMID: 15905523]
[http://dx.doi.org/10.4049/jimmunol.174.11.6820] [PMID: 15905523]
[31]
Lee FI, Brain AT. Chronic diffuse interstitial pulmonary fibrosis and rheumatoid arthritis. Lancet 1962; 2(7258): 693-5.
[http://dx.doi.org/10.1016/S0140-6736(62)90505-6] [PMID: 13929074]
[http://dx.doi.org/10.1016/S0140-6736(62)90505-6] [PMID: 13929074]
[32]
Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford) 2002; 41(9): 972-80.
[http://dx.doi.org/10.1093/rheumatology/41.9.972] [PMID: 12209029]
[http://dx.doi.org/10.1093/rheumatology/41.9.972] [PMID: 12209029]
[33]
Naldini A, Filippi I, Miglietta D, Moschetta M, Giavazzi R, Carraro F. Interleukin-1β regulates the migratory potential of MDAMB231 breast cancer cells through the hypoxia-inducible factor-1α. Eur J Cancer 2010; 46(18): 3400-8.
[http://dx.doi.org/10.1016/j.ejca.2010.07.044] [PMID: 20801015]
[http://dx.doi.org/10.1016/j.ejca.2010.07.044] [PMID: 20801015]
[34]
Lewis AM, Varghese S, Xu H, Alexander HR. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 2006; 4: 48.
[http://dx.doi.org/10.1186/1479-5876-4-48] [PMID: 17096856]
[http://dx.doi.org/10.1186/1479-5876-4-48] [PMID: 17096856]
[35]
Kumar S, Kishimoto H, Chua HL, et al. Interleukin-1 alpha promotes tumor growth and cachexia in MCF-7 xenograft model of breast cancer. Am J Pathol 2003; 163(6): 2531-41.
[http://dx.doi.org/10.1016/S0002-9440(10)63608-5] [PMID: 14633625]
[http://dx.doi.org/10.1016/S0002-9440(10)63608-5] [PMID: 14633625]
[36]
Perrier S, Caldefie-Chézet F, Vasson MP. IL-1 family in breast cancer: potential interplay with leptin and other adipocytokines. FEBS Lett 2009; 583(2): 259-65.
[http://dx.doi.org/10.1016/j.febslet.2008.12.030] [PMID: 19111549]
[http://dx.doi.org/10.1016/j.febslet.2008.12.030] [PMID: 19111549]
[37]
Zhou W, Guo S, Gonzalez-Perez RR. Leptin pro-angiogenic signature in breast cancer is linked to IL-1 signalling. Br J Cancer 2011; 104(1): 128-37.
[http://dx.doi.org/10.1038/sj.bjc.6606013] [PMID: 21139583]
[http://dx.doi.org/10.1038/sj.bjc.6606013] [PMID: 21139583]
[38]
Saliba E, Henrot A. Inflammatory mediators and neonatal brain damage. Biol Neonate 2001; 79(3-4): 224-7.
[http://dx.doi.org/10.1159/000047096] [PMID: 11275656]
[http://dx.doi.org/10.1159/000047096] [PMID: 11275656]
[39]
Touzani O, Boutin H, Chuquet J, Rothwell N. Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J Neuroimmunol 1999; 100(1-2): 203-15.
[http://dx.doi.org/10.1016/S0165-5728(99)00202-7] [PMID: 10695731]
[http://dx.doi.org/10.1016/S0165-5728(99)00202-7] [PMID: 10695731]
[40]
Gasche Y, Fujimura M, Morita-Fujimura Y, et al. Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 1999; 19(9): 1020-8.
[http://dx.doi.org/10.1097/00004647-199909000-00010] [PMID: 10478654]
[http://dx.doi.org/10.1097/00004647-199909000-00010] [PMID: 10478654]
[41]
Bartha JL, Romero-Carmona R, Escobar-Llompart M, Comino-Delgado R. The relationships between leptin and inflammatory cytokines in women with pre-eclampsia. BJOG 2001; 108(12): 1272-6.
[http://dx.doi.org/10.1111/j.1471-0528.2001.00284.x] [PMID: 11843390]
[http://dx.doi.org/10.1111/j.1471-0528.2001.00284.x] [PMID: 11843390]
[42]
Dicou E, Attoub S, Gressens P. Neuroprotective effects of leptin in vivo and in vitro. Neuroreport 2001; 12(18): 3947-51.
[http://dx.doi.org/10.1097/00001756-200112210-00019] [PMID: 11742217]
[http://dx.doi.org/10.1097/00001756-200112210-00019] [PMID: 11742217]
[43]
Girard J. Is leptin the link between obesity and insulin resistance? Diabetes Metabolism 1997; 23 Suppl 3(5): 16.
[44]
Torpy DJ, Bornstein SR, Chrousos GP. Leptin and interleukin-6 in sepsis. Horm Metab Res 1998; 30(12): 726-9.
[http://dx.doi.org/10.1055/s-2007-978967] [PMID: 9930630]
[http://dx.doi.org/10.1055/s-2007-978967] [PMID: 9930630]
[45]
Kettritz R, Choi M, Rolle S, Wellner M, Luft FC. Integrins and cytokines activate nuclear transcription factor-kappaB in human neutrophils. J Biol Chem 2004; 279(4): 2657-65.
[http://dx.doi.org/10.1074/jbc.M309778200] [PMID: 14613935]
[http://dx.doi.org/10.1074/jbc.M309778200] [PMID: 14613935]
[46]
Reape TJ, Groot PH. Chemokines and atherosclerosis. Atherosclerosis 1999; 147(2): 213-25.
[http://dx.doi.org/10.1016/S0021-9150(99)00346-9] [PMID: 10559506]
[http://dx.doi.org/10.1016/S0021-9150(99)00346-9] [PMID: 10559506]
[47]
Bruun JM, Verdich C, Toubro S, Astrup A, Richelsen B. Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men. Eur J Endocrinol 2003; 148(5): 535-42.
[http://dx.doi.org/10.1530/eje.0.1480535] [PMID: 12720537]
[http://dx.doi.org/10.1530/eje.0.1480535] [PMID: 12720537]
[48]
Straczkowski M, Dzienis-Straczkowska S, Stêpieñ A, Kowalska I, Szelachowska M, Kinalska I. Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-α system. J Clin Endocrinol Metab 2002; 87(10): 4602-6.
[http://dx.doi.org/10.1210/jc.2002-020135] [PMID: 12364441]
[http://dx.doi.org/10.1210/jc.2002-020135] [PMID: 12364441]
[49]
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112(12): 1796-808.
[http://dx.doi.org/10.1172/JCI200319246] [PMID: 14679176]
[http://dx.doi.org/10.1172/JCI200319246] [PMID: 14679176]
[50]
Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112(12): 1821-30.
[http://dx.doi.org/10.1172/JCI200319451] [PMID: 14679177]
[http://dx.doi.org/10.1172/JCI200319451] [PMID: 14679177]
[51]
Bruun JM, Pedersen SB, Richelsen B. Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. J Clin Endocrinol Metab 2001; 86(3): 1267-73.
[http://dx.doi.org/10.1210/jc.86.3.1267] [PMID: 11238519]
[http://dx.doi.org/10.1210/jc.86.3.1267] [PMID: 11238519]
[52]
Chabaud M, Durand JM, Buchs N, et al. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 1999; 42(5): 963-70.
[http://dx.doi.org/10.1002/1529-0131(199905)42:5<963: AID-ANR15>3.0.CO;2-E] [PMID: 10323452]
[http://dx.doi.org/10.1002/1529-0131(199905)42:5<963: AID-ANR15>3.0.CO;2-E] [PMID: 10323452]
[53]
Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. J Immunol 2003; 170(5): 2655-62.
[http://dx.doi.org/10.4049/jimmunol.170.5.2655] [PMID: 12594294]
[http://dx.doi.org/10.4049/jimmunol.170.5.2655] [PMID: 12594294]
[54]
Appel H, Maier R, Wu P, et al. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther 2011; 13(3): R95.
[http://dx.doi.org/10.1186/ar3370] [PMID: 21689402]
[http://dx.doi.org/10.1186/ar3370] [PMID: 21689402]
[55]
Wang YH, Wills-Karp M. The potential role of interleukin-17 in severe asthma. Curr Allergy Asthma Rep 2011; 11(5): 388-94.
[http://dx.doi.org/10.1007/s11882-011-0210-y] [PMID: 21773747]
[http://dx.doi.org/10.1007/s11882-011-0210-y] [PMID: 21773747]
[56]
Bullens DMA, Truyen E, Coteur L, et al. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res 2006; 7(1): 135.
[http://dx.doi.org/10.1186/1465-9921-7-135] [PMID: 17083726]
[http://dx.doi.org/10.1186/1465-9921-7-135] [PMID: 17083726]
[57]
Felderhoff-Mueser U, Schmidt O I, Oberholzer A, et al. A key player in neuroinflammation and neurodegeneration? Trends in Neurosciences 2005; 28(9): 0-493.
[58]
Harms RZ, Yarde DN, Guinn Z, et al. Increased expression of IL-18 in the serum and islets of type 1 diabetics. Mol Immunol 2015; 64(2): 306-12.
[http://dx.doi.org/10.1016/j.molimm.2014.12.012] [PMID: 25576800]
[http://dx.doi.org/10.1016/j.molimm.2014.12.012] [PMID: 25576800]
[59]
Jitprasertwong P, Jaedicke KM, Nile CJ, Preshaw PM, Taylor JJ. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine 2014; 65(2): 222-30.
[http://dx.doi.org/10.1016/j.cyto.2013.10.008] [PMID: 24275551]
[http://dx.doi.org/10.1016/j.cyto.2013.10.008] [PMID: 24275551]
[60]
Yin N, Wang D, Zhang H, et al. Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin. Cancer Res 2004; 64(16): 5870-5.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0655] [PMID: 15313931]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0655] [PMID: 15313931]
[61]
Yu K. Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway. Mol Med Rep 2013.
[PMID: 24213635]
[PMID: 24213635]
[62]
Matarese G. Leptin and the immune system: how nutritional status influences the immune response. Eur Cytokine Netw 2000; 11(1): 7-14.
[PMID: 10705294]
[PMID: 10705294]
[63]
Matarese G, Di Giacomo A, Sanna V, et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 2001; 166(10): 5909-16.
[http://dx.doi.org/10.4049/jimmunol.166.10.5909] [PMID: 11342605]
[http://dx.doi.org/10.4049/jimmunol.166.10.5909] [PMID: 11342605]
[64]
Busso N, So A, Chobaz-Péclat V, et al. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol 2002; 168(2): 875-82.
[http://dx.doi.org/10.4049/jimmunol.168.2.875] [PMID: 11777985]
[http://dx.doi.org/10.4049/jimmunol.168.2.875] [PMID: 11777985]
[65]
La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol 2004; 4(5): 371-9.
[http://dx.doi.org/10.1038/nri1350] [PMID: 15122202]
[http://dx.doi.org/10.1038/nri1350] [PMID: 15122202]
[67]
Mancuso P, McNish RW, Peters-Golden M, Brock TG. Evaluation of phagocytosis and arachidonate metabolism by alveolar macrophages and recruited neutrophils from F344xBN rats of different ages. Mech Ageing Dev 2001; 122(15): 1899-913.
[http://dx.doi.org/10.1016/S0047-6374(01)00322-0] [PMID: 11557288]
[http://dx.doi.org/10.1016/S0047-6374(01)00322-0] [PMID: 11557288]
[68]
Mancuso P, Canetti C, Gottschalk A, Tithof PK, Peters-Golden M. Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein expression. Am J Physiol Lung Cell Mol Physiol 2004; 287(3): L497-502.
[http://dx.doi.org/10.1152/ajplung.00010.2004] [PMID: 15145787]
[http://dx.doi.org/10.1152/ajplung.00010.2004] [PMID: 15145787]
[69]
Zarkesh-Esfahani H, Pockley G, Metcalfe RA, et al. High-dose leptin activates human leukocytes via receptor expression on monocytes. J Immunol 2001; 167(8): 4593-9.
[http://dx.doi.org/10.4049/jimmunol.167.8.4593] [PMID: 11591788]
[http://dx.doi.org/10.4049/jimmunol.167.8.4593] [PMID: 11591788]
[70]
Loffreda S, Yang SQ, Lin HZ, et al. Leptin regulates proinflammatory immune responses. FASEB J 1998; 12(1): 57-65.
[http://dx.doi.org/10.1096/fasebj.12.1.57] [PMID: 9438411]
[http://dx.doi.org/10.1096/fasebj.12.1.57] [PMID: 9438411]
[71]
Gainsford T, Willson TA, Metcalf D, et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA 1996; 93(25): 14564-8.
[http://dx.doi.org/10.1073/pnas.93.25.14564] [PMID: 8962092]
[http://dx.doi.org/10.1073/pnas.93.25.14564] [PMID: 8962092]
[72]
Zarkesh-Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJ. Leptin indirectly activates human neutrophils via induction of TNF-α. J Immunol 2004; 172(3): 1809-14.
[http://dx.doi.org/10.4049/jimmunol.172.3.1809] [PMID: 14734764]
[http://dx.doi.org/10.4049/jimmunol.172.3.1809] [PMID: 14734764]
[73]
Caldefie-Chezet F, Poulin A, Vasson MP. Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic Res 2003; 37(8): 809-14.
[http://dx.doi.org/10.1080/1071576031000097526] [PMID: 14567439]
[http://dx.doi.org/10.1080/1071576031000097526] [PMID: 14567439]
[74]
Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol 2005; 174(6): 3137-42.
[http://dx.doi.org/10.4049/jimmunol.174.6.3137] [PMID: 15749839]
[http://dx.doi.org/10.4049/jimmunol.174.6.3137] [PMID: 15749839]
[75]
Ottonello L, Gnerre P, Bertolotto M, et al. Leptin as a uremic toxin interferes with neutrophil chemotaxis. J Am Soc Nephrol 2004; 15(9): 2366-72.
[http://dx.doi.org/10.1097/01.ASN.0000139321.98029.40] [PMID: 15339985]
[http://dx.doi.org/10.1097/01.ASN.0000139321.98029.40] [PMID: 15339985]
[76]
Tian Z, Sun R, Wei H, et al. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun 2002; 298(3): 0-302.
[77]
Lam QL, Liu S, Cao X, Lu L. Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Eur J Immunol 2006; 36(12): 3118-30.
[http://dx.doi.org/10.1002/eji.200636602] [PMID: 17125143]
[http://dx.doi.org/10.1002/eji.200636602] [PMID: 17125143]
[78]
Mattioli B, Giordani L, Quaranta MG, Viora M. Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3K-Akt signaling pathway. FEBS Lett 2009; 583(7): 1102-6.
[http://dx.doi.org/10.1016/j.febslet.2009.02.029] [PMID: 19250936]
[http://dx.doi.org/10.1016/j.febslet.2009.02.029] [PMID: 19250936]
[79]
Lam QLK, Zheng BJ, Jin DY, et al. Leptin Induces CD40 Expression through the Activation of Akt in Murine Dendritic Cells. J Biol Chem 2007; 282(38): 27587-97.
[80]
Lam QL, Liu S, Cao X, Lu L. Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Eur J Immunol 2006; 36(12): 3118-30.
[http://dx.doi.org/10.1002/eji.200636602] [PMID: 17125143]
[http://dx.doi.org/10.1002/eji.200636602] [PMID: 17125143]
[81]
Tian Z, Sun R, Wei H, Gao B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun 2002; 298(3): 297-302.
[http://dx.doi.org/10.1016/S0006-291X(02)02462-2] [PMID: 12413939]
[http://dx.doi.org/10.1016/S0006-291X(02)02462-2] [PMID: 12413939]
[82]
Zhao Y, Sun R, You L, et al. Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun 2003; 300(2): 0-252.
[83]
Lo CK, Lam QL, Yang M, et al. Leptin signaling protects NK cells from apoptosis during development in mouse bone marrow. Cell Mol Immunol 2009; 6(5): 353-60.
[http://dx.doi.org/10.1038/cmi.2009.46] [PMID: 19887048]
[http://dx.doi.org/10.1038/cmi.2009.46] [PMID: 19887048]
[84]
La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol 2004; 4(5): 371-9.
[http://dx.doi.org/10.1038/nri1350] [PMID: 15122202]
[http://dx.doi.org/10.1038/nri1350] [PMID: 15122202]
[85]
Martín-Romero C1. Santos-Alvarez J, Goberna R, Sánchez-Margalet V. Human leptin enhances activation and proliferation of human circulating t lymphocytes. Cell Immunol 2000; 199(1): 15-24.
[86]
Matarese G, Di Giacomo A, Sanna V, et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 2001; 166(10): 5909-16.
[http://dx.doi.org/10.4049/jimmunol.166.10.5909] [PMID: 11342605]
[http://dx.doi.org/10.4049/jimmunol.166.10.5909] [PMID: 11342605]
[87]
De Rosa V, Procaccini C, Calì G, et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity 2007; 26(2): 241-55.
[http://dx.doi.org/10.1016/j.immuni.2007.01.011] [PMID: 17307705]
[http://dx.doi.org/10.1016/j.immuni.2007.01.011] [PMID: 17307705]
[88]
Procaccini C, De Rosa V, Galgani M, et al. Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses. J Immunol 2012; 189(6): 2941-53.
[http://dx.doi.org/10.4049/jimmunol.1200935] [PMID: 22904304]
[http://dx.doi.org/10.4049/jimmunol.1200935] [PMID: 22904304]
[89]
Procaccini C, De Rosa V, Galgani M, et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 2010; 33(6): 929-41.
[http://dx.doi.org/10.1016/j.immuni.2010.11.024] [PMID: 21145759]
[http://dx.doi.org/10.1016/j.immuni.2010.11.024] [PMID: 21145759]
[90]
Matarese G, Carrieri PB, La Cava A, et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci USA 2005; 102(14): 5150-5.
[http://dx.doi.org/10.1073/pnas.0408995102] [PMID: 15788534]
[http://dx.doi.org/10.1073/pnas.0408995102] [PMID: 15788534]
[91]
Agrawal S, Gollapudi S, Su H, Gupta S. Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J Clin Immunol 2011; 31(3): 472-8.
[http://dx.doi.org/10.1007/s10875-010-9507-1] [PMID: 21243519]
[http://dx.doi.org/10.1007/s10875-010-9507-1] [PMID: 21243519]
Article Metrics
33
6
1
1