The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation

Group IIA secreted phospholipase A2 controls skin carcinogenesis and psoriasis by shaping the gut microbiota

“…In the accompanying paper ( 75 ), Doré et al have found that PLA2G2A TGN mice on a C57BL/6 genetic background exhibited age-associated systemic inflammation with lymphomegaly, granulocytosis, elevation of circulating IL-17A, and increased arthritis, due to alteration of the gut microbiota and bacteria-derived lipids. As in the case of Pla2g2a –/– mice shown here, the phenotypes in PLA2G2A TGN mice are less severe after treatment with antibiotics or after housing in a more stringent SPF facility and can be modified by fecal transfer (cohousing in our study) through oral gavage.…”

Regulatory Roles of Phospholipase A2 Enzymes and Bioactive Lipids in Mast Cell Biology

“…Indeed, metagenome analysis of the stool revealed that several bacterial genera such as Gram-positive Lachnospiraceae and Ruminococcaceae and Gram-negative Helicobacteraceae and Prevotellaceae are differently distributed in Pla2g2a +/+ and Pla2g2a –/– mice, and there is a better correlation between distinct PCA responses and Ruminococcaceae and Mucispirillum abundances in the two facilities. The alteration in gut microbiota in Pla2g2a –/– BALB/c mice, as well as in PLA2G2A -transgenic C57BL/6 mice in which human sPLA 2 -IIA is overexpressed systemically, also impact the severity of arthritis and psoriasis ( 22 , 132 ). Thus, sPLA 2 -IIA acts as a host factor that is primarily expressed in the intestine and contributes to shaping of the gut microbiota, whose disturbance by Pla2g2a deletion or overexpression secondarily affects various diseases including those involving mast cells in proximal and distal tissues ( Figure 5B ).…”

Recent progress of nanomedicine in secreted phospholipase A2 as a potential therapeutic target

“…Some sPLA2s even participate in the immune processes, and some may lead to severe obesity. 9,10 Moreover, phospholipid hydrolysates are involved in tissue and nerve injury, as well as a series of inflammation and neurological disorders. Under pathological conditions, sPLA2 can be induced by multiple cascades and effector molecules.…”