The role of the adipocyte and adiponectin in the regulation of innate immune response
Abstract
Adipocytes have the potential to regulate immune response by expressing toll receptors and inflammatory cytokines. The regulation of immune response in adipocytes is unclear. We found that adipocytes directly respond to LPS and activate NFκB DNA binding and luciferase reporter (P < 0.05). LPS also induced IL-6 gene and protein expression in both primary pig adipocytes and 3T3-L1 cells (P < 0.05). Unlike IL-6, TNFα expression was not inducible in pig adipocytes by LPS after 8 hours, but LPS induced TNFα expression in 3T3-L1 after 24 hours exposure (P < 0.05). Inhibition of MEK, PKC, p38 MAPK, JNK and inhibitory G protein (Gi) with U0126, bisindolylmaleimide, SB203580, SP600125 and pertussis toxin respectively, showed that inhibition of MEK, PKC and Gi suppressed IL-6 expression (P < 0.05). Adiponectin also reduced the DNA binding of NFκB and reporter activation in pig adipocytes and 3T3-L1, respectively (P < 0.05). The regulation of IL-6 by adiponectin is cell type specific. In pig adipocytes, adiponectin suppressed its gene expression (P < 0.05) but not its protein expression (P > 0.05), but in 3T3-L1, adiponectin suppressed IL-6 protein (P < 0.05) but not its gene expression (P > 0.05). However, in 3T3-Ll, adiponectin suppressed both the gene expression (P < 0.05) and media protein accumulation (P < 0.065) of TNFα.
Adipocytes could potentially regulate memory T cell formation and muscle growth by expressing IL15. IFNγ induces IL-15 mRNA (P < 0.05) in pig adipocytes, but its expression was inhibited by PKC inhibition (P < 0.05). IL-15 also stimulates lipolysis in a PKA and JAK/STAT dependent manner (P < 0.05). Fatty acids have been shown to induce inflammation in muscle and macrophages. In adipocytes, palmitate but not laurate and docosahexaenoic acid (DHA) induced the activation of NFκB and IL-6 expression (P < 0.05). Inhibition of palmitate activation with triacsin C, additively with palmitate induced the activation of NFκB luciferase and IL-6 expression (P < 0.05). Additionally, phosphatidyl inositol 3 kinase (PI3K) inhibitor (wortmannin) induced luciferase reporter activation and IL-6 gene expression, alone and additively with palmitate (P < 0.05). Overall, these data indicate that the adipocyte is capable of responding to pathogen structures like LPS and to fatty acids and cytokines like IFNγ to release other cytokines that have immunological functions such as IL-6, TNFα and IL-15. Finally, adiponectin suppresses LPS-induced cytokine expression in adipocytes.
Degree
Ph.D.
Advisors
Spurlock, Purdue University.
Subject Area
Livestock|Anatomy & physiology|Animals
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