Hydrogen sulphide induces mouse paw oedema through activation of phospholipase A2.
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.
di Villa Bianca
Roberta d'Emmanuele
Rd
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Coletta
Ciro
C
Mitidieri
Emma
E
De Dominicis
Gianfranco
G
Rossi
Antonietta
A
Sautebin
Lidia
L
Cirino
Giuseppe
G
Bucci
Mariarosaria
M
Sorrentino
Raffaella
R
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
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
Br J Pharmacol. 2005 May;145(2):141-4
15753944
FASEB J. 2005 Jul;19(9):1196-8
15863703
J Biochem. 2002 Mar;131(3):285-92
11872155
Curr Opin Pharmacol. 2006 Apr;6(2):125-9
16487749
Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H474-80
12124191
Br J Pharmacol. 2009 Nov;158 Suppl 1:S1-254
19883461
J Pharmacol Exp Ther. 2006 Aug;318(2):611-8
16644903
Pancreas. 2008 May;36(4):e24-31
18437075
J Infect. 2003 Aug;47(2):155-60
12860150
Br J Pharmacol. 2004 May;142(2):331-8
15155540
Curr Top Med Chem. 2007;7(8):811-20
17456044
Br J Pharmacol. 1978 Apr;62(4):481-6
656694
FASEB J. 2005 Apr;19(6):623-5
15671155
Cancer Res. 1990 Nov 1;50(21):6966-70
2170013
Toxicon. 2000 Feb;38(2):199-208
10665801
Antioxid Redox Signal. 2010 May 15;12(10):1191-202
19803739
Neuroscience. 2008 Mar 3;152(1):89-96
18248901
Inflamm Res. 2008 Nov;57(11):512-8
19109743
J Cell Biochem. 1989 Jun;40(2):147-55
2768346
J Exp Med. 1996 Mar 1;183(3):821-7
8642286
FASEB J. 2006 Oct;20(12):2118-20
16912151
Br J Pharmacol. 2004 Dec;143(7):881-9
15504752