Peptidoglycan recognition protein 3 (PglyRP3) has an anti-inflammatory role in intestinal epithelial cells

Abstract

Intestinal epithelial cells produce cytokines in response to bacterial peptidoglycan (PGN), which is detected by several classes of pattern-recognition receptors (PRRs) as peptidoglycan recognition proteins (PGlyRPs), Toll-like receptor 2 (TLR2) and NOD receptors. All types of PGlyRPs recognize bacterial peptidoglycan and function in antibacterial innate immunity. In this study, we investigated the role of PGlyRP3 in the response of intestinal epithelial cells (Caco-2) to PGN from pathogenic (Staphylococcus aureus), opportunistic pathogenic (Micrococcus luteus) and non-pathogenic (Bacillus subtilis and Lactobacillus rhamnosus GG) bacteria found in the gut as commensals or in gastroenteritis. All PGNs induced the proinflammatory cytokines IL-12p35, IL-8 and TNF-α and, time-dependently, PGlyRP3, at both the transcription and protein levels. In this context, no differences were observed among the distinct PGN obtained from different bacterial sources. The inflammatory response to PGN is mediated via the TLR2 pathway, since blocking this pathway by inhibiting MyD88 reduced the expression of proinflammatory cytokines. In addition, PGlyRP3 overexpression suppressed, while PGlyRP3 knocking down enhanced the expression of PGN-induced inflammatory cytokines. It is concluded that PGN stimulates inflammatory responses in the intestinal epithelia through activation of the TLR pathway. PGlyRP3 is also stimulated by PGN and has, in contrast to activation of the TLR pathway, an anti-inflammatory effect.