Inhibition of chemokine expression in rat inflamed paws by systemic use of the antihyperalgesic oxidized ATP.
BACKGROUND
We previously showed that local use of periodate oxidized ATP (oATP, a selective inhibitor of P2X7 receptors for ATP) in rat paw treated with Freund's adjuvant induced a significant reduction of hyperalgesia Herein we investigate the role of oATP, in the rat paws inflamed by carrageenan, which mimics acute inflammation in humans.


RESULTS
Local, oral or intravenous administration of a single dose of oATP significantly reduced thermal hyperalgesia in hind paws of rats for 24 hours, and such effect was greater than that induced by diclofenac or indomethacin. Following oATP treatment, the expression of the pro-inflammatory chemokines interferon-gamma-inducible protein-10 (IP-10), mon ocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) within the inflamed tissues markedly decreased on vessels and infiltrated cells. In parallel, the immunohistochemical findings showed an impairment, with respect to the untreated rats, in P2X7 expression, mainly on nerves and vessels close to the site of inflammation. Finally, oATP treatment significantly reduced the presence of infiltrating inflammatory macrophages in the paw tissue.


CONCLUSIONS
Taken together these results clearly show that oATP reduces carrageenan-induced inflammation in rats.
Fulgenzi
Alessandro
A
Università degli Studi di Milano, Istituto di Patologia Generale, via Mangiagalli 31, 20133, Milano, Italy. mariaelena.ferrero@unimi.it.
Dell'Antonio
Giacomo
G
Foglieni
Chiara
C
Dal Cin
Elena
E
Ticozzi
Paolo
P
Franzone
Josè S
JS
Ferrero
Maria Elena
ME
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D000279:Administration, Cutaneous; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan / Q000633:toxicity; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000235:genetics; D058486:Receptors, Purinergic P2X7; D016037:Single-Blind Method
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016209:Interleukin-8; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D004008:Diclofenac; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate; D002351:Carrageenan; D007213:Indomethacin