Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin‐induced asthma model through the induction of regulatory T cells

Abstract

Bee venom (BV) is one of the alternative medicines that have been widely used in the treatment of chronic inflammatory diseases. We previously demonstrated that BV induces immune tolerance by increasing the population of regulatory T cells (Tregs) in immune disorders. However, the major component and how it regulates the immune response have not been elucidated. We investigated whether bee venom phospholipase A2 (bvPLA2) exerts protective effects that are mediated via Tregs in OVA‐induced asthma model. bvPLA2 was administered by intraperitoneal injection into control and OVA‐challenged mice. The Treg population, total and differential bronchoalveolar lavage fluid (BALF) cell count, Th2 cytokines, and lung histological features were assessed. Treg depletion was used to determine the involvement of Treg migration and the reduction of asthmatic symptoms. The CD206‐dependence of bvPLA2‐treated suppression of airway inflammation was evaluated in OVA‐challenged CD206‐/‐ mice. The bvPLA2 treatment induced the Tregs and reduced the infiltration of inflammatory cells into the lung in the OVA‐challenged mice. Th2 cytokines in the bronchoalveolar lavage fluid (BALF) were reduced in bvPLA2‐treated mice. Although bvPLA2 suppressed the number of inflammatory cells after OVA challenge, these effects were not observed in Treg‐depleted mice. In addition, we investigated the involvement of CD206 in bvPLA2‐mediated immune tolerance in OVA‐induced asthma model. We observed a significant reduction in the levels of Th2 cytokines and inflammatory cells in the BALF of bvPLA2‐treated OVA‐induced mice but not in bvPLA2‐treated OVA‐induced CD206‐/‐ mice. These results demonstrated that bvPLA2 can mitigate airway inflammation by the induction of Tregs in an OVA‐induced asthma model.

Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice

“…In contrast, our study demonstrated that increased AHR and the Th2 type cytokine productions were diminished by intratracheal injection of bvPLA2 in the OVA-challenged mice. In addition, our previous study demonstrated that Th2 cytokines, such as IL-4, IL-5, and IL-13, were inhibited by intraperitoneal administration of bvPLA2 in the OVA-induced airway inflammation mouse model [11]. Our results suggest that bvPLA2 plays an important role in Th2 responses during sensitization.…”

“…Furthermore, we found that PLA2 is the active compound in bee venom capable for modulating the Treg populations, both in vitro and in vivo [9,10,11]. PLA2 from bee venom belongs to group III secreted PLA2 (sPLA2) enzymes, which play important roles in a wide range of cellular functions, including phospholipid metabolism, signal transduction, and inflammatory and immune responses [27].…”

“…In the previous report, bvPLA2 had an inhibitory effect on OVA-induced allergic airway inflammation through the induction of regulatory T cells [11]. The exact mechanisms underlying the suppressive role of intratracheal administered bvPLA2 during the development of allergic asthma are yet to be defined.…”

“…This study was performed as previously reported with minor modifications [11]. Briefly, the mice were sensitized by intraperitoneal (i.p.)…”

“…Bee venom PLA2 (bvPLA2) is one of the major components of bee venom [8]. Our previous studies reported that bvPLA2 directly bound to the CD206 mannose receptor, which promoted immune tolerance through Treg cells modulation and prevented various inflammatory responses, such as neuroinflammation, airway inflammation, and acute kidney injury [9,10,11]. To study the impact of the route of administration on bvPLA2 penetration into the lungs, bvPLA2 was delivered by intratracheal instillation in an OVA-challenged allergic airway inflammation mouse model.…”