NLRP3 inflammasome is involved in testicular inflammation induced by lipopolysaccharide in mice

Abstract

Problem Systemic inflammation induced by infection, which is associated with testicular inflammation, predisposes males to subfertility. Recently, the nucleotide‐binding oligomerization domain, leucine‐rich repeat‐, and pyrin domain‐containing 3 (NLRP3) inflammasome was identified as a key mediator of inflammation, and excessive activation of the NLRP3 inflammasome was shown to contribute to the pathogenesis of a wide variety of diseases. However, the mechanisms underlying infectious inflammation in the testis remain unclear. We investigated the effect of lipopolysaccharide (LPS)‐induced systemic inflammation on the role of the NLRP3 inflammasome in murine testes. Method of study We performed in vivo and in vitro studies using an LPS‐induced model of NLRP3 inflammasome activation and testicular inflammation. Results Intraperitoneal administration of LPS significantly impaired sperm motility in the epididymis of wild type (WT) and NLRP3‐knockout (KO) mice. LPS administration stimulated interleukin (IL)‐1β production and secretion in the testes of WT mice, and these adverse effects were improved in the testes of NLRP3‐KO mice. LPS administration also stimulated neutrophil infiltration as well as its chemoattractant C‐C motif chemokine ligand 2 (CCL2) in WT testes, which were suppressed in NLRP3‐KO testes. In in vitro cell culture, treatment with LPS and NLRP3 inflammasome activation significantly induced IL‐1β and CCL2 secretion from WT but not NLRP3‐KO testicular cells. Conclusions Taken together, our results suggest that testicular cells have the potential to secrete IL‐1β and CCL2 in an NLRP3 inflammasome‐dependent manner and that these cytokines from the testis may further exacerbate testicular function, resulting in subfertility during infectious diseases.

TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor‐1α

“…Recently, empagliflozin (EMPA), a selective inhibitor of the sodium glucose co‐transporter 2, which reduced the risk of hospitalization for heart failure and cardiovascular death in type 2 diabetic patients in the EMPA‐REG OUTCOME trial, 41,42 has been found to improve myocardial strain, and reduces cardiac pro‐inflammatory cytokines via regulating NLRP3 and MyD88‐related pathways in nondiabetic mice treated with doxorubicin 43 . While, activation of NLRP3 or MyD88‐related pathways induces Ccl2 expression 44,45 . Whether the cardioprotective effect of EMPA is also related to inhibition of macrophages infiltration should be studied further.…”

Insight toward inflammasome complex contribution to male infertility

“…However, comparing NLRP‐3 KO animal testicular cell culture results with wild LPS‐induced mice cells revealed significantly lower levels, indicating the point that NLRP‐3 plays a major role in IL‐1β activation (not the only activator, but probably the main one). Thus, the author suggests that the NLRP‐3 plays a vital role in testicular inflammation condition, in which inhibiting this complex may result in ameliorated testicular inflammation 84 …”

“…Thus, the author suggests that the NLRP-3 plays a vital role in testicular inflammation condition, in which inhibiting this complex may result in ameliorated testicular inflammation. 84…”

Developmental and reproductive toxic effects of exposure to microplastics: A review of associated signaling pathways

“…NLRP3, NOD-like receptor protein 3, is a multi-protein that acts as the defense mechanism against microorganisms, endogenous damage, and toxic stimuli but is also involved in male and female infertility ( de Rivero Vaccari, 2020 ; Sano et al, 2022 ). The activation of NLRP3 triggers an apoptotic and inflammatory response by converting pro-caspase-1 to caspase-1 and pro-interleukin-1 (pro-IL-1β) and pro-interleukin-18 (pro-IL-18) into interleukin-1β (IL-1β) and interleukin-18 (IL-18), respectively ( Charan et al, 2022 ).…”