Distribution and regulation of cyclooxygenase‐2 in carrageenan‐induced inflammation

Abstract

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute in¯ammation, carrageenan-induced paw údema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw údema) and high doses (hyperalgesia). COX-2 and prostaglandin E 2 (PGE 2 ) levels were measured by RT ± PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a signi®cant and parallel induction of both COX-2 and PGE 2 . This induction was signi®cantly higher in hyperalgesia than in paw údema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and in¯ammatory cells of rats experiencing hyperalgesia. In paw údema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw údema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw údema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.

Inhibitory Effects of Ginsenoside Rb1,Rg3, and Panax ginseng Head Butanol Fraction on Inflammatory Mediators from LPS-Stimulated RAW 264.7 Cells

“…Additionally, in rheumatoid arthritis, it is known that the third phase of the edema-induced by carrageenan, in which the edema reaches its highest volume, is characterized by the presence of prostaglandins (Spector and Willoughb, 1963). Besides, in the carrageenaninduced rat paw edema model, the production of prostanoids has been through the serum expression of COX-2 by a positive feedback mechanism (Nantel et al, 1999).…”

Evaluation of Anti-Inflammatory Activity of Pseudananas macrodontes (Morr.) Harms (Bromeliaceae) Fruit Extract in Rats

“…The initial phase of edema formation (0 -1 h), which is not inhibited by NSAIDs, is attributed to the release of histamine and serotonin (Di Rosa et al, 1971). The second phase (1 -6 h) is associated with a local infi ltration and activation of neutrophils (Boughton-Smith et al, 1993) and the production of prostaglandins (Di Rosa et al, 1971), which has been attributed to the induction of COX-2 ( Nantel et al, 1999). An increase in NO production is also associated with the increase of paw volume (Salvemini et al, 1996).…”

Anti-Inflammatory Activity of Methanolic Leaf Extract of Kigelia Africana (Lam.) Benth and Stem Bark Extract of Acacia Hockii De Wild in Mice

“…The NSAIDs less inhibit the initial phase of carrageenan-induced paw edema, and this is attributed to the release of histamine, serotonin and bradykinin. However, the second phase is attributed to the induction of inducible COX-2 and can be blocked using NSAIDs [37]. It is therefore believed that the anti-inflammatory activities of leaf extract of K. africana and stem bark extract of A. hockii, inhibited the synthesis and release of prostaglandins to manage edema.…”