Affected inflammation-related signaling pathways in snake envenomation: A recent insight

Abstract

Snake envenomation is well known to cause grievous pathological signs, including haemorrhagic discharge, necrosis, and respiratory distress. However, inflammatory reactions are also common envenoming manifestations that lead to successive damage, such as oedema, ulceration, lymphadenectasis, systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Interference with the inflammatory burst is hence important in the clinical treatment of snake envenomation. Here, we summarize the typical snake toxins (or venoms) that cause inflammatory reactions and the underlying signaling pathways. In brief, inflammatory reactions are usually triggered by snake venom phospholipase A2 (svPLA2), snake venom metalloprotease (SVMP), snake venom serine protease (SVSP) and C-type lectin/snaclec (CTL) as well as disintegrin (DIS) via multiple signaling pathways. They are nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducer and activator of transcription (JAK-STAT) and phosphoinositide 3-Kinase/protein kinase B (PI3K/PKB also called PI3K-AKT) signaling pathways. Activation of these pathways promotes the expression of pro-inflammatory molecules such as cytokines, especially interleukin-1β (IL-1β) which causes further inflammatory cascades and manifestations, such as swelling, fever, pain, and severe complications. Remarkably, almost half of introduced snake toxins (or venoms) have anti-inflammatory effects through blocking these pathways and suppressing the expression of pro-inflammatory molecules. Investigation of affected inflammation-related signaling pathways is meaningful to achieve better clinical treatment.

Keywords: Inflammasome; JAK-STAT; MAPK; NF-κB; PI3K-AKT; Snake envenomation.