TY - JOUR
T1 - IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes
AU - Shinjo, Takanori
AU - Iwashita, Misaki
AU - Yamashita, Akiko
AU - Sano, Tomomi
AU - Tsuruta, Mitsudai
AU - Matsunaga, Hiroaki
AU - Sanui, Terukazu
AU - Asano, Tomoichiro
AU - Nishimura, Fusanori
N1 - Funding Information:
This study was supported by Kyushu University Interdisciplinary Programs in Education and Projects in Research Development ( FB79495910 ).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/19
Y1 - 2016/8/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2016.06.049
DO - 10.1016/j.bbrc.2016.06.049
M3 - Article
C2 - 27311858
AN - SCOPUS:84976613049
SN - 0006-291X
VL - 477
SP - 241
EP - 246
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
