Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in rat chronic granulomatous inflammation.
Chronic inflammation, a condition frequently associated with several pathologies, is characterized by angiogenic and fibrogenic responses that may account for the development of granulomatous tissue. We previously demonstrated that the chymase, rat mast cell protease-5 (rMCP-5), exhibits pro-inflammatory and pro-angiogenic properties in a model of chronic inflammation sustained by mast cells (MCs), granuloma induced by the subcutaneous carrageenan-soaked sponge implant in rat. In this study, we investigated the effects of palmitoylethanolamide (PEA), an anti-inflammatory and analgesic endogenous compound, on rMCP-5 mRNA expression and Microphtalmia-associated Transcription Factor (MITF) activation in the same model of chronic inflammation. The levels of rMCP-5 mRNA were detected using semi-quantitative RT-PCR; the protein expression of chymase and extracellular signal-regulated kinases (ERK) were analyzed by western blot; MITF/DNA binding activity and MITF phosphorylation were assessed by electrophoretic mobility shift assay (EMSA) and immunoprecipitation, respectively. The administration of PEA (200, 400 and 800 µg/ml) significantly decreased rMCP-5 mRNA and chymase protein expression induced by λ-carrageenan. These effects were associated with a significant decrease of MITF/DNA binding activity and phosphorylated MITF as well as phosphorylated ERK levels. In conclusion, our results, showing the ability of PEA to inhibit MITF activation and chymase expression in granulomatous tissue, may yield new insights into the understanding of the signaling pathways leading to MITF activation controlled by PEA.
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Daniele
D
De Filippis
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Annapina
A
Russo
European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Via Olgettina, 58, 20132 Milan, Italy.
Daniela
D
De Stefano
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Mariateresa
M
Cipriano
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini, 5, 80131 Naples, Italy.
Davide
D
Esposito
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Gianluca
G
Grassia
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Rosa
R
Carnuccio
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
Giulia
G
Russo
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy. Electronic address: iuvone@unina.it.
Teresa
T
Iuvone
D000577:Amides; D000818:Animals; D002351:Carrageenan / Q000009:adverse effects; D002908:Chronic Disease; D053818:Chymases / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D063388:Endocannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects*; D006099:Granuloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects
D000577:Amides; D063388:Endocannabinoids; D004983:Ethanolamines; D051739:Microphthalmia-Associated Transcription Factor; D010169:Palmitic Acids; C005958:palmidrol; D002351:Carrageenan; D004247:DNA; D048052:Mitogen-Activated Protein Kinase 3; D053818:Chymases; C509228:Cma1 protein, rat
Chronic inflammation; Microphtalmia-associated Transcription Factor; Palmitoylethanolamide; Rat mast cell protease