Bee Venom Induces Acute Inflammation through a H2O2-Mediated System That Utilizes Superoxide Dismutase

Abstract

Venoms from venomous arthropods, including bees, typically induce an immediate local inflammatory response; however, how venoms acutely elicit inflammatory response and which components induce an inflammatory response remain unknown. Moreover, the presence of superoxide dismutase (SOD3) in venom and its functional link to the acute inflammatory response has not been determined to date. Here, we confirmed that SOD3 in bee venom (bvSOD3) acts as an inducer of H2O2 production to promote acute inflammatory responses. In mouse models, exogenous bvSOD3 rapidly induced H2O2 overproduction through superoxides that are endogenously produced by melittin and phospholipase A2, which then upregulated caspase-1 activation and proinflammatory molecule secretion and promoted an acute inflammatory response. We also showed that the relatively severe noxious effect of bvSOD3 elevated a type 2 immune response and bvSOD3 immunization protected against venom-induced inflammation. Our findings provide a novel view of the mechanism underlying bee venom-induced acute inflammation and offer a new approach to therapeutic treatments for bee envenoming and bee venom preparations for venom therapy/immunotherapy.

Antioxidant Activity and Mechanism of Action of Amwaprin: A Protein in Honeybee (Apis mellifera) Venom

“…We demonstrated that during oxidative stress, the increase in cell viability in the presence of Amwaprin was due to the inhibition of caspase-3 activity by Amwaprin. Although honeybee venom typically causes inflammatory responses [5,28,35], its administration in alternative therapy exhibits anti-inflammatory effects [4,7]. H 2 O 2 is a well-known mediator of inflammation [36][37][38][39][40].…”

“…The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were determined using ELISA Kits (Abcam, Cambridge, UK). NIH-3T3 cells were cultured in 96-well plates (2 × 10 4 cells/well) and treated with 250 ng/mL recombinant Amwaprin and 50 µM H 2 O 2 for 24 or 48 h. The ELISA assays were performed as described in our previous study [28]. Briefly, the media from the treated NIH-3T3 cells was collected and added to each well of a 96-well plate coated with an anti-mouse IL-1β, IL-6, or TNF-α antibody (Abcam).…”

“…In addition to the identification of new proteins, such as Amwaprin and superoxide dismutase [18,28], novel functions of known honeybee venom components, including secapin, serine protease, protease inhibitors, and major royal jelly proteins 8-9, have also been characterized [8,9,13,29,30]. Current research on honeybee venom is directed toward its pharmacological and toxicological effects [4][5][6]10,11,28,30]. For instance, despite a previous study demonstrating significant anti-cancer activity of melittin against malignant melanoma, melittin is widely known for its strong hemolytic activity [11].…”

The Future of Leishmaniasis Treatment: Protein Targets and Beyond

“…Likewise, in plants, PLA2 contributes to pathogen defense and stress response, enabling plants to adapt and survive adverse conditions. [156][157][158][159][160][161][162] It is important to note that while secondary metabolites like venoms can be harmful, they may also have beneficial functions such as protection against pathogens, symbiotic interactions, or chemical communication. However, venom production is primarily associated with defense and capturing prey.…”

The Future of Leishmaniasis Treatment: Protein Targets and Beyond

“…Likewise, in plants, PLA2 contributes to pathogen defense and stress response, enabling plants to adapt and survive adverse conditions. [158][159][160][161][162][163][164] It's essential to recognize that while secondary metabolites like venoms can pose risks, they can also serve beneficial roles, such as safeguarding against pathogens, fostering symbiotic interactions, or facilitating chemical communication. Nevertheless, the primary function of venom production is often linked to defense and the capture of prey.…”