Testosterone enhances lipopolysaccharide-induced interleukin-6 and macrophage chemotactic protein-1 expression by activating the extracellular signal-regulated kinase 1/2/nuclear factor-κB signalling pathways in 3T3-L1 adipocytes.
Low-grade chronic inflammation is commonly found in patients with polycystic ovary syndrome (PCOS) who exhibit hyperandrogenism or hyperandrogenemia. Clinical studies have shown that hyperandrogenemia is closely correlated with low-grade chronic inflammation. However, the mechanism underlying this correlation remains unclear. Recent studies have suggested that adipocytes increase the production of proinflammatory mediators such as interleukin-6 (IL-6) and macrophage chemotactic protein-1 (MCP-1) when the inflammatory signal transduction cascade system is activated by external stimuli. The present study aimed to evaluate the effects of testosterone on the innate signalling and expression of proinflammatory mediators in 3T3-L1 adipocytes, which were or were not induced by lipopolysaccharide (LPS). The effects of testosterone on the expression of proinflammatory mediators, nuclear factor-κB (NF-κB), and extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways were investigated using an enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, western blot analysis and an electrophoresis mobility shift assay. Testosterone induces IL-6 and MCP-1, and enhances LPS-induction of IL-6 and MCP-1. However, the effects are not simply additive, testosterone significantly enhanced the effects of LPS-induced inflammation factors. Testosterone induces the phosphorylation of ERK1/2 and NF-κB. The effect of testosterone on the expression of IL-6 and MCP-1 is inhibited by PD98059 , an ERK1/2 inhibitor, and PDTC, an NF-κB inhibitor. The results indicate that testosterone enhances LPS-induced IL-6 and MCP-1 expression by activating the ERK1/2/NF-κB signalling pathways in 3T3-L1 adipocytes.
Department of Gynecology, Shanghai Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai 200011, P.R. China.
Chunlin
C
Su
Department of Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Min
M
Chen
Key Laboratory of Molecular Medicine Ministry of Education, Shanghai Medical University Affliated to Fudan University, Shanghai 200011, P.R. China.
Haiyan
H
Huang
Department of Gynecology, Shanghai Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai 200011, P.R. China.
Jinfang
J
Lin
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives; D013739:Testosterone / Q000008:administration & dosage* / Q000378:metabolism; D013859:Thiocarbamates / Q000008:administration & dosage
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005419:Flavonoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D013739:Testosterone; D011392:Proline; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one