The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors.

Baumann, Heinz; Morella, Karen K.; White, David W.; Dembski, Marlene; Bailon, Pascal; Kim, Hongkyun; Lai, Chun-Fai; Tartaglia, Louis A.

doi:10.1073/pnas.93.16.8374

Cited by 749 publications

(543 citation statements)

References 32 publications

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“…The OSMRP and the OB-R are related to gp130 in primary structure (23.3% and 20.7% overall amino acid identity, respectively) and in modular structure, featuring both Ig-like and FN III domains (Hibi et al, 1990;Tartaglia et al, 1995;Mosley et al, 1996). While the OB-R and gp130, at least in part, activate overlapping intracellular signaling molecules, gp130 does not form part of the receptor-complex of leptin (Baumann et al, 1996a).…”

Section: The Il-6 Signal Transduce< Gp130mentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-1 1, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affhity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

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Section: The Il-6 Signal Transduce< Gp130mentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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“…structure, consisting of four interconnected antiparallel a-helices, is highly similar to members of the long-chain helical cytokines, such as interleukin-6 (IL-6), IL-11, IL-12, and granulocyte colony-stimulating factor. 17,18 As an endocrine hormone, leptin is synthesized mainly by adipose tissue and, more particularly, by differentiated mature adipocytes. Circulating levels and adipose tissue mRNA expression of leptin are proportionate to the body mass index (BMI) and the body fat mass.…”

Section: Introductionmentioning

confidence: 99%

Leptin in immuno-rheumatological diseases

et al. 2011

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Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders. Keywords: adipokines; autoimmune diseases; leptin; rheumatic diseases INTRODUCTIONThe existence of a factor secreted by white adipose tissue (WAT), which acts to control feeding, weight and WAT mass, was first proposed by Kennedy 1 and is supported by monogenic mutations resulting in obesity. [2][3][4] WAT is composed of adipocytes filled mainly with triacylglycerol and embedded in loose connective tissue containing adipocyte precursors, fibroblasts, immune and other cells. Obesity, the condition that originally motivated the research on WAT, is characterized by low-grade systemic inflammation. It is thought that excess WAT can contribute to the maintenance of obesity through inflammation-inducing lipotoxicity by secreting factors that stimulate the synthesis of inflammatory agents in other organs and by secreting inflammatory agents itself. 5 The current view of WAT states that it is an active contributor to body homeostasis by sending out and responding to signals that modulate appetite, energy expenditure, insulin sensitivity, the endocrine and reproductive systems, bone metabolism, inflammation and immunity. 6 Several findings have converged to indicate that adipocytes share certain properties with immune cells, such as complement activation 7 and proinflammatory cytokine production. 8 Fat cell precursors also share features with macrophages. Numerous genes that code for transcription factors, cytokines, inflammatory signaling molecules, and fatty acid transporters are essential for adipocyte biology and are also expressed and functional in macrophages. 9 Adipose tissue secrets a variety of factors: the term 'adipokine' is generally given to any protein that can be synthesized and secreted by adipocytes. Among these factors, only leptin and adiponectin (and possibly resistin, adipsi...

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“…In the recent years, accumulating evidence has established the role of leptin as a growth factor that modulates immune responses [2,3]. The structure of leptin has high similarity to members of the long-chain helical cytokines such as IL-6, IL-11, IL-12, G-CSF, leukemia inhibitory factor and oncostatin [4,5]. Several studies have revealed an important role for leptin in regulating lymphopoiesis and hematopoiesis [1,2,[6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…In relation to the important function of leptin in immune responses, leptin receptor (Ob-R) expression has been found not only in the central nervous system but also in peripheral lymphoid tissues and hematopoietic stem cells [2,8,12]. Encoded by the diabetes (db) gene, the Ob-R is a member of the class I cytokine receptors, which have the signaling capability of IL-6-type cytokine receptors [4]. Ob-R mRNA gives rise to six different forms of the receptor by alternative splicing, but only the long isoform (Ob-Rb) has been recognized to be of importance in leptin-mediated signaling [1].…”

Section: Introductionmentioning

confidence: 99%

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

et al. 2006

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Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IjB-a. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation.See accompanying commentary: http://dx

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The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors.

Cited by 749 publications

References 32 publications

Interleukin‐6: Structure‐function relationships

Interleukin‐6: Structure‐function relationships

Leptin in immuno-rheumatological diseases

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

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