Anti-Macrophage monoclonal antibody [FITC]

Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin D (GSDMD)mediated membrane pore formation, cell swelling and rapid lysis, followed by the massive release of pro-inflammatory mediators such as interleukin-1 beta and interleukin-18. There are two main pathways of pyroptosis: the caspase-1-mediated canonical pathway and the caspase-4/5/11-mediated noncanonical pathway. However, the caspase-3-gasdermin E (GSDME) pathway and caspase-8-GSDMD pathway also induce pyroptosis. Pyroptosis can not only cause local inflammation but also lead to amplification of the inflammatory response. Recent studies have suggested that pyroptosis is closely related with cardiovascular disease (CVD); for example, in atherosclerosis, myocardial infarction, ischemia-reperfusion injury, heart failure, coronary calcification and aortic aneurysm, study results have promoted the development of inhibitors targeting the components related to pyroptosis, and some agents have been clinically proven to have cardiovascular benefits. In this review, we summarize emerging evidence to discuss the progressive understanding of pyroptosis and the pathways, effect and effectors of pyroptosis, as well as the role of pyroptosis in CVD. Additionally, we summarize pyroptosis-related pathway inhibitors and classic cardiovascular drugs targeting pyroptosis.

Background and Purpose The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in neuropathic pain remain elusive. Experimental Approach Male rats and wild-type and TRPV1 knockout mice with peripheral nerve injury - sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice - provided models of chronic neuropathic pain. Ipsilateral lumbar (L)4-5 DRGs were assayed for activin C expression. Chronic neuropathic pain animals were treated with intrathecal or locally pre-administered activin C or the vehicle. Nociceptive behaviours and pain-related markers in L4-5 DRGs and spinal cord were evaluated. TRPV1 channel modulation by activin C was measured. Key Results Following peripheral nerve injury, expression of activin beta C subunit mRNA and activin C protein was markedly up-regulated in L4-5 DRGs of animals (with CCI). Intrathecal activin C dose-dependently inhibited neuropathic pain in spinal nerve ligated rats. Local pre-administration of activin C decreased neuropathic pain, macrophage infiltration into ipsilateral L4-5 DRGs and microglial reaction in L4-5 spinal cords of mice with CCI. In rat DRG neurons, activin C enhanced capsaicin-induced TRPV1 currents. Pre-treatment with activin C reduced capsaicin-evoked acute hyperalgesia and normalized capsaicin-evoked persistent hypothermia in mice. Finally, the analgesic effect of activin C was abolished in TRPV1 knockout mice with CCI. Conclusion and Implications Activin C inhibits neuropathic pain by modulating TRPV1 channels, revealing potential analgesic applications in chronic neuropathic pain therapy.