Fatty acid ethanolamides acting on proliferator-activated receptor (PPAR)-α are among the endogenous lipid molecules that attenuate inflammatory processes and pain sensitivity. Whereas these properties are well-known for palmitoylethanolamide (PEA), the efficacy of oleoylethanolamide (OEA, first described as a satiety hormone synthesized in the jejunum) has been overlooked. In this study, we aimed to evaluate the effect of OEA administration in a mouse model of colitis. C57BL/6J mice were exposed to 2.5% dextran sodium sulphate (DSS) in drinking water for 5 days. Daily i.p. administration of 10 mg/kg OEA started 3 days before DSS and lasted for 12 days. The DSS-untreated control group received only ultrapure water. DSS mice treated with OEA had a significant improvement of disease score. OEA restored mRNA transcription of PPAR-α, of tight junctions and protective factors of colon integrity disrupted by DSS. The improvement correlated with significant decrease of colonic and systemic levels of pro-inflammatory cytokines compared to the DSS group. OEA antiinflammatory effects were mediated by the selective targeting of the TLR4 axis causing a downstream inhibition of nuclear factor kappa B (NF-κB)- MyD88-dependent and NLRP3 inflammation pathways. OEA treatment also inhibited DSS-induced increase of inflammatory cytokines levels in the mesenteric lymph nodes. Conclusions and implications: These results underscore the validity of OEA as a potent protective and anti-inflammatory agent in ulcerative colitis that may be exploited to broaden the pharmacological strategies against inflammatory bowel disease.

The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice / Adriano Lama, Gustavo Provensi, Roberta Amoriello, Claudio Pirozzi, Barbara Rani, Maria Pina Mollica, Giuseppina Mattace Raso, Clara Ballerini, Rosaria Meli, Maria Beatrice Passani. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - STAMPA. - 129:(2020), pp. 1-8. [10.1016/j.biopha.2020.110368]

The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice

Gustavo Provensi;Roberta Amoriello;Barbara Rani;Clara Ballerini;Maria Beatrice Passani
2020

Abstract

Fatty acid ethanolamides acting on proliferator-activated receptor (PPAR)-α are among the endogenous lipid molecules that attenuate inflammatory processes and pain sensitivity. Whereas these properties are well-known for palmitoylethanolamide (PEA), the efficacy of oleoylethanolamide (OEA, first described as a satiety hormone synthesized in the jejunum) has been overlooked. In this study, we aimed to evaluate the effect of OEA administration in a mouse model of colitis. C57BL/6J mice were exposed to 2.5% dextran sodium sulphate (DSS) in drinking water for 5 days. Daily i.p. administration of 10 mg/kg OEA started 3 days before DSS and lasted for 12 days. The DSS-untreated control group received only ultrapure water. DSS mice treated with OEA had a significant improvement of disease score. OEA restored mRNA transcription of PPAR-α, of tight junctions and protective factors of colon integrity disrupted by DSS. The improvement correlated with significant decrease of colonic and systemic levels of pro-inflammatory cytokines compared to the DSS group. OEA antiinflammatory effects were mediated by the selective targeting of the TLR4 axis causing a downstream inhibition of nuclear factor kappa B (NF-κB)- MyD88-dependent and NLRP3 inflammation pathways. OEA treatment also inhibited DSS-induced increase of inflammatory cytokines levels in the mesenteric lymph nodes. Conclusions and implications: These results underscore the validity of OEA as a potent protective and anti-inflammatory agent in ulcerative colitis that may be exploited to broaden the pharmacological strategies against inflammatory bowel disease.
129
1
8
Goal 3: Good health and well-being
Adriano Lama, Gustavo Provensi, Roberta Amoriello, Claudio Pirozzi, Barbara Rani, Maria Pina Mollica, Giuseppina Mattace Raso, Clara Ballerini, Rosaria Meli, Maria Beatrice Passani
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1197845
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