期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 501, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.110654
关键词
Calcium sensing receptor; Preadipocytes; Macrophages; Crosstalk; NLRP3 inflammasome
资金
- FONDECYT [1150651]
- CONICYT [21140284, 22170739]
Excess adipose tissue (AT) associates with inflammation and obesity-related diseases. We studied whether calcium-sensing receptor (CaSR)-mediated NLRP3 inflammasome activation in THP-1 macrophages elevates inflammation in LS14 preadipocytes, modeling deleterious AT cell crosstalk. THP-1 macrophages exposed to cinacalcet (CaSR activator, 2 mu M, 4 h) showed elevated proinflammatory marker and NLRP3 inflammasome mRNA, pro-IL-1 beta protein and caspase-1 activity, whereas preincubation with CaSR negative modulators prevented these effects. The key NLRP3 inflammasome component ASC was silenced (siRNA) in THP-1 cells, and inflammasome activation was evaluated (qPCR, Western blot, caspase-1 activity) or they were further cultured to obtain conditioned medium (CoM). Exposure of LS14 preadipocytes to CoM from cinacalcet-treated THP-1 elevated LS14 proinflammatory cytokine expression, which was abrogated by THP-1 inflammasome silencing. Thus, CaSR activation elevates THP-1-induced inflammation in LS14 preadipocytes, via macrophage NLRP3 inflammasome activation. Modulating CaSR activation may prevent deleterious proinflammatory cell crosstalk in AT, a promising approach in obesity-related metabolic disorders.
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