Prolactin inhibits or stimulates the inflammatory response of joint tissues in a cytokine-dependent manner

Endocrinology. 2023 Oct 21:bqad156. doi: 10.1210/endocr/bqad156. Online ahead of print.ABSTRACTThe close association between rheumatoid arthritis (RA), sex, reproductive state, and stress has long linked prolactin (PRL) to disease progression. PRL has both proinflammatory and anti-inflammatory outcomes in RA, but responsible mechanisms are not understood. Here, we show that PRL modifies in an opposite manner the proinflammatory actions of IL-1β and TNF-α in mouse synovial fibroblasts (SF) in culture. Both IL-1β and TNF-α upregulated the metabolic activity and the expression of proinflammatory factors (Il1b, Inos, and Il6) via the activation of the NF-κB signaling pathway. However, IL-1β increased and TNF-α decreased the levels of the long PRL receptor isoform in association with dual actions of PRL on SF inflammatory response. PRL reduced the proinflammatory effect and activation of NF-κB by IL-1β but increased TNF-α-induced inflammation and NF-κB signaling. The double-faceted role of PRL against the two cytokines manifested also in vivo. IL-1β or TNF-α with or without PRL were injected into the knee joints of healthy mice and joint inflammation was monitored after 24 hours. IL-1β and TNF-α increased the joint expression of proinflammatory factors and the infiltration of immune cells. PRL prevented the actions of IL-1β but was either inactive or further increased the proinflammatory effect of TNF-α. We conclude that PRL exerts opposite actions on joint inflam...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research