title: Hydrogen sulphide induces mouse paw oedema through activation of phospholipase A2.
abstract: OBJECTIVE
  Hydrogen sulphide (H(2)S), considered as a novel gas transmitter, is produced endogenously in mammalian tissue from L-cysteine by two enzymes, cystathionine β-synthase and cystathionine γ-lyase. Recently, it has been reported that H(2)S contributes to the local and systemic inflammation in several experimental animal models. We conducted this study to investigate on the signalling involved in H(2)S-induced inflammation.
  
  
  METHODS
  L-cysteine or sodium hydrogen sulphide (NaHS) was injected into the mouse hind paw and oedema formation was evaluated for 60 min. In order to investigate H(2)S-induced oedema formation, we used 5-HT and histamine receptor antagonists, and inhibitors of K(ATP) channels or arachidonic acid cascade. Prostaglandin levels were determined in hind paw exudates by radioimmunoassay. Paws injected with L-cysteine or NaHS were examined by histological methods.
  
  
  RESULTS
  Both NaHS and L-cysteine caused oedema characterized by a fast onset which peaked at 30 min. This oedematogenic action was not associated with histamine or 5-HT release or K(ATP) channel activation. However, oedema formation was significantly inhibited by the inhibition of cyclooxygenases and selective inhibition of phospholipase A(2). Prostaglandin levels were significantly increased in exudates of hind paw injected with NaHS or L-cysteine. The histological examination clearly showed an inflammatory state with a loss of tissue organization following NaHS or L-cysteine injection.
  
  
  CONCLUSIONS
  Phospholipase A(2) and prostaglandin production are involved in pro-inflammatory effects of H(2)S in mouse hind paws. The present study contributes to the understanding of the role of L-cysteine/H(2)S pathway in inflammatory disease.
authors.affiliation: Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
authors.forename: Roberta d'Emmanuele
authors.initials: Rd
authors.lastname: di Villa Bianca
authors.forename: Ciro
authors.initials: C
authors.lastname: Coletta
authors.forename: Emma
authors.initials: E
authors.lastname: Mitidieri
authors.forename: Gianfranco
authors.initials: G
authors.lastname: De Dominicis
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Bucci
authors.forename: Raffaella
authors.initials: R
authors.lastname: Sorrentino
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005528:Foot / Q000473:pathology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides
chemical_list: D016861:Cyclooxygenase Inhibitors; D064801:Phospholipase A2 Inhibitors; D011453:Prostaglandins; D013440:Sulfides; D003533:Cyproheptadine; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D003545:Cysteine; D006862:Hydrogen Sulfide
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