Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils

Abstract

Basophils have been erroneously considered as minor relatives of mast cells, due to some phenotypic similarity between them. While recent studies have revealed non-redundant roles for basophils in various immune responses, basophil-derived effector molecules, including lipid mediators, remain poorly characterized, compared to mast cell-derived ones. Here we analyzed and compared eicosanoids produced by mouse basophils and mast cells when stimulated with IgE plus allergens. The production of 5-LOX metabolites such as LTB4 and 5-HETE was detected as early as 0.5 h post-stimulation in both cell types, even though their amounts were much smaller in basophils than in mast cells. In contrast, basophils and mast cells showed distinct time course in the production of COX metabolites, including PGD2, PGE2 and 11-HETE. Their production by mast cells was detected at both 0.5 and 6 h post-stimulation while that by basophils was detectable only at 6 h. Of note, mast cells showed 8–9 times higher levels of COX-1 than did basophils at the resting status. In contrast to unaltered COX-1 expression with or without stimulation, COX-2 expression was up-regulated in both cell types upon activation. Importantly, when activated, basophils expressed 4–5 times higher levels of COX-2 than did mast cells. In accordance with these findings, the late-phase production of the COX metabolites by basophils was completely ablated by COX-2 inhibitor whereas the early-phase production by mast cells was blocked by COX-1 but not COX-2 inhibitor. Thus, the production of COX metabolites is differentially regulated by COX-1 and COX-2 in basophils and mast cells.

Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction

“…Further, the severity of IBS-D with abdominal pain is directly proportional to the amounts of prostaglandin E2 (PGE2) released [17,18]. A key step involving in PGE2 production is the conversion of arachidonic acid to prostanoids catalyzed by cyclooxygenase-1 and-2 (COX-1, COX-2) [19]. Previous study have shown that 6-gingerol can inhibit the production of PGE2 and inflammation [20].…”

The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations

“…Chronic inflammation is associated with factors like reactive species of oxygen and nitrogen, cytokines, chemokines, growth factors, and specific microRNAs, which often contribute to cancer development [19]. In most epithelial cells, COX-2 is absent or expressed at low levels but is a major contributor to inflammation and is up-regulated in many cancers, [20], so it is a relevant therapeutic target for cancer prevention and treatment [10,11,12,13]. Studies in K14-HPV16 mice have demonstrated that COX-2 is overexpressed in skin lesions induced by the HPV16 early genes [20].…”

“…HPV-induced multiphase carcinogenesis is often associated with chronic inflammation, and experimental studies in HPV transgenic mice suggest that inflammatory phenomena play an essential role in the development of intraepithelial and invasive lesions [9]. Cyclooxygenase-2 (COX-2), a key mediator of inflammation, is involved in the development of multiple types of cancer, such as colon cancer, making it a useful therapeutic target [10,11,12,13]. We have previously shown that a specific COX-2 inhibitor, celecoxib, was able to block the progression of HPV16-induced lesions in transgenic mice [14].…”

Is There a Role for Basophils in Cancer?

“…Both human and mouse basophils rapidly synthesize cysteinyl leukotriene C 4 (LTC 4 ) through the 5-lipoxygenase pathway (83). There is evidence that mouse basophils metabolize arachidonic acid through cyclooxygenase activity to form prostaglandin D 2 (PGD 2 ) and prostaglandin E 2 (PGE 2 ) (72,84). In contrast, there is currently no solid evidence that highly purified human basophils can produce measurable levels of PGD 2, or any other lipid mediator generated through the cyclooxygenase pathway (85).…”

“… ND, not done . a Several key surface markers are used to characterize human [IgE + , FcεRI + , CCR3 + , (CD123)IL-3Rα + , CD63 + , CD203c + ] ( 15 , 36 , 57 , 61 , 71 ) and murine basophils (FcεRI + , KIT − , CD49b + , CD200R3 + ) ( 35 , 62 , 72 – 76 ) by flow cytometric analysis . b This table essentially includes the phenotypic characteristics of peripheral blood human and mouse basophils.…”