Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 29, Issue 2, Pages 622-627Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2015.09.019
Keywords
Phospholipase C; U73122; Scavenger receptors; Pro-inflammatory cytokines
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Funding
- National Natural Science Foundation of China [31472172]
- State Key Laboratory of Veterinary Etiological Biology [SKLVEB2014KFKT005]
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A wide range of biological processes are controlled by phospholipase C (PLC)/Ca(2 +) signaling, which could be blocked by PLC-specific inhibitor U73122. Whether inhibition of PLC with chemical inhibitor U73122 affects the inflammatory response in monocytes/macrophages is currently unknown. In this study, we demonstrated that U73122 inhibited PMA-induced in vitro differentiation of human promonocytic U937 cells into macrophages as reflected by the reduction of cell adherence and the decreased expression of macrophage specific marker CD163. It is possible that U73122 blocked PMA-induced adhesion of U937 cells partially by down regulation and inactivation of both Pyk2 and paxillin signaling. Furthermore, the expression of LPS-induced proinflammatory cytokines TNF-alpha and IL-1 beta was significantly blocked by U73122 in both dU937 cells and mouse primary peritoneal macrophages. These results suggest that PLC is involved in the sophisticated inflammatory response by monocytes/macrophages, and thereby chemical antagonists of PLC may be potential agents for the suppression of inflammatory response. (C) 2015 Elsevier B.V. All rights reserved.
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