Peroxisome proliferator‐activated receptor‐β/δ modulates mast cell phenotype

Abstract

The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is known to have multiple anti-inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ mice expressed higher levels of high-affinity IgE receptor (FcεRI) compared with Pparβ/δ mice. BMMCs from Pparβ/δ mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ mice. Resting BMMCs from Pparβ/δ mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal-regulated kinases compared with Pparβ/δ mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype.

The role of peroxisome proliferator-activated receptors (PPAR) in immune responses

“…The antiinflammatory effects of PPARβ/δ are also exhibited in mast cells. Mast cells from PPARβ/δ KO mice express higher levels of inflammatory cytokines and lower levels of high-affinity IgE receptor compared to WT [88].…”

Non‐IgE mediated mast cell activation

“…A recent study showed that BMMCs and peritoneal MCs from Ppar β / δ +/+ mice expressed higher levels of FcεRI compared with Ppar β / δ −/− mice. Furthermore, the development and maturation of peritoneal MCs was markedly impaired in the KO mice with several proteases, but also beta‐hexosaminidase content being significantly diminished in cultured BMMCs . Interestingly, cytokine production was differentially affected depending on the type of stimulus (IgE/Ag, UVB, LPS, or TPA).…”

“…Furthermore, the development and maturation of peritoneal MCs was markedly impaired in the KO mice with several proteases, but also beta-hexosaminidase content being significantly diminished in cultured BMMCs. 242 Interestingly, cytokine production was differentially affected depending on the type of stimulus (IgE/Ag, UVB, LPS, or TPA). alarmins can either restore homeostasis or provoke uncontrolled inflammation.…”

The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension

“…The splanchnic mast cells, behaving as a metabolic sensor in chronic hepatic insufficiency, would have a modulating behavior of these metabolic alterations [41]. In particular, two functions that are severely impaired in chronic liver disease, like the detoxing function made by the Kupffer cells, and the antioxidant function, mediated by the peroxisomes [42], could be partially improved by the compensating actions of the mast cells [43] (Figure 6). Furthermore, the splanchnic mast cells could develop metabolic functions that adapt to this new metabolic environment.…”

“…Peroxisomal disorders are inherent to the hepatic dysfunction [57]. However, peroxisome proliferator-activated receptor-beta/delta (PPAR-β/δ) and PPAR-alpha with multiple anti-inflammatory effects could modulate the mast cell phenotype reducing the levels of inflammatory cytokines in liver chronic diseases [43,58,59].…”