IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes

Takanori Shinjo, Misaki Iwashita, Akiko Yamashita, Tomomi Sano, Mitsudai Tsuruta, Hiroaki Matsunaga, Terukazu Sanui, Tomoichiro Asano, Fusanori Nishimura

Research output: Contribution to journalArticle

Abstract

Interleukin-17A (IL-17A) is known to induce inflammatory responses and to be involved in the pathogenesis of not only autoimmune diseases, but also several metabolic and infectious diseases. In this study, IL-17A is shown to induce IL-6 expression in 3T3-L1 mature adipocytes. Interestingly, we found that IL-17A synergistically amplified TNFα-induced secretion of IL-6 and upregulation of IL-17RA expression in 3T3-L1 adipocytes. Its synergistic effects on IL-6 production were inhibited by pre-treatment with inhibitors of IκBα and JNK. Furthermore, IL-17A cooperatively enhanced LPS-mediated IL-6 production in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. In addition, IL-17A also enhanced CCL20 production in 3T3-L1 adipocytes stimulated with TNFα or co-cultured with LPS-stimulated RAW macrophages. In high-fat diet-fed mouse epididymal adipose tissues, IL-17RA and RORγt mRNA levels were significantly increased and the serum level of CCL20 was also upregulated. Taken together, these data show that, in adipose tissues, IL-17A contributes to exacerbating insulin resistance-enhancing IL-6 production and promotes the infiltration of Th17 cells in cooperation with TNFα; these findings represent a novel hypothesis for the association between IL-17A-producing cells and type 2 diabetes.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number2
DOIs
Publication statusPublished - Aug 19 2016

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Interleukin-17
Adipocytes
Interleukin-6
Macrophages
Adipose Tissue
Tissue
Metabolic Diseases
High Fat Diet
Nutrition
Medical problems
Infiltration
Type 2 Diabetes Mellitus
Autoimmune Diseases
Communicable Diseases
Insulin Resistance
Up-Regulation
Fats
Insulin
Messenger RNA
Serum

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes. / Shinjo, Takanori; Iwashita, Misaki; Yamashita, Akiko; Sano, Tomomi; Tsuruta, Mitsudai; Matsunaga, Hiroaki; Sanui, Terukazu; Asano, Tomoichiro; Nishimura, Fusanori.

In: Biochemical and Biophysical Research Communications, Vol. 477, No. 2, 19.08.2016, p. 241-246.

Research output: Contribution to journalArticle

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