Patulin inhibits LPS-induced nitric oxide production by suppressing MAPKs signaling pathway

Abstract

Patulin (PAT) is a natural product isolated from several species of fungi. Here, we evaluated the effect of PAT (62.5–4,000 ng/ml) in lipopolysaccharide (LPS)-activated murine peritoneal macrophages. Cell viability assay showed that PAT at concentrations up to 250 ng/ml did not affect macrophage viability. PAT (250 ng/ml) significantly reduced LPS-induced nitric oxide production (by 98.4%), inducible nitric oxide synthase (iNOS) expression (by 83.5%), and iNOS messenger ribonucleic acid expression (by 100.0%). Moreover, PAT significantly reduced LPS-induced interleukin-1β (by 80.6%), cluster of differentiation (CD) 69 (by 63.1%), and Toll-like receptor (TLR) 4 (by 91.9%) protein expression. Finally, PAT significantly reduced LPS-triggered phosphorylation of all mitogen-activated protein kinases (MAPK) assessed: extracellular signal-regulated kinase (ERK; by 89.5%), c-Jun N-terminal kinase (JNK; by 77.5%), and p38 (by 72.3%). Taken together, these data suggest that PAT downregulates acute inflammatory response, inhibiting nitric oxide production by suppressing CD69-TLR4/ERK-JNK-p38 MAPKs/Nos2/iNOS signaling pathway.

Graphical Abstract

Keywords:

• 4-hydroxy-4H-furo(3,2-C)-pyran-2(6H)-one
• clavacin
• macrophage
• acute inflammation

Disclosure statement

No potential competing interest was reported by the authors.

Additional information

Funding

This work was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES)/National Program of Academic Cooperation (PROCAD) under Grant 2951/2014 and the National Council for Scientific and Technological Development (CNPq) under Grant 154801/2019-4.