Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation

Abstract

The effects of topical application of arachidonic acid (AA) or phorbol ester, tetradecanoylphorbol 13-acetate (TPA), on edema response, vascular permeability, MPO, NAG, and generation of eicosanoids were studied in two murine models of cutaneous inflammation. AA produced a short-lived edema response with a rapid onset that was associated with marked increases in levels of prostaglandins (PGE2, 6-keto-PGF1 alpha, PGF2 alpha), thromboxane B2 (TxB2) and leukotriene B4 (LTB4), with smaller increases in levels of LTC4. TPA produced a longer-lasting edema that was associated with marked influx of neutrophils and predominant formation of LTB4 along with significant changes in levels of TxB2. Circulating T lymphocytes have no apparent role in the acute inflammatory responses induced by either agent. Arachidonic acid-induced vascular permeability preceded the edema response and neutrophil influx, whereas TPA-induced vascular permeability paralleled the edema response and influx of neutrophils. Mast cells appear to be important in the complete expression of inflammatory response, i.e., edema, cellular influx, and vascular permeability induced by either AA or TPA, as these responses were blunted in mast cell-deficient mice. Inhibitors of CO or 5-LO attenuated inflammatory responses in both models. The LTB4 receptor antagonist, SC-41930, inhibited the inflammatory response to TPA but had little effect on that initiated by AA. This suggests that LTB4 is an important mediator in the phorbol ester-induced inflammatory response, whereas peptidoleukotrienes and prostaglandins regulate vascular permeability responses in the arachidonate model.

Prostaglandin E2–EP3 Signaling Induces Inflammatory Swelling by Mast Cell Activation

“…Role of PGE 2 -EP3 signaling in AA-induced and PGE 2 -induced hyperpermeability It was previously reported that lipid mediators synthesized by COX pathways are involved in AA-induced inflammation, and that PGE 2 was abundantly synthesized within ear tissues upon AA application (37). Indeed, also in our experimental settings, aspirin significantly suppressed AA-induced hyperpermeability (Fig.…”

“…1E). Application of AA has been shown to induce the production of a broad range of eicosanoids such as PGE 2 (37). We therefore examined the direct effect of exogenous PGE 2 on vascular permeability.…”

“…MC-derived inflammatory mediators such as histamine and proteases have been shown to increase vascular permeability. Indeed, MCs were reported to be essential for Ag-independent inflammation, such as AA-induced inflammation and irritant contact dermatitis (19,37). We therefore examined the effects of genetic depletion of MCs (W/W v ) on AA-induced hyperpermeability.…”

In vivoanti-inflammatory properties of aerial parts ofNasturtium officinale

“…This enzyme activates other enzymatic pathways such as phospholipase A2 (PLA2) and mitogen activated protein kinases (MAPK), resulting in release of platelet activation factor (PAF) and arachidonic acid. These events either induce vasodilatation, vascular permeability, and secretion of serotonin and histamine or stimulate synthesis of prostaglandins and leukotrienes by cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) enzymes, respectively (Carlson et al, 1985;Fischer et al, 1988;Rao et al, 1993). Based on this, one possible mechanism for the anti-inflammatory effects of the extract, in the TPA model, is its interaction with the infiltration of leucocytes (according to the pathological results) and regulation of release or function of inflammatory eicosanoids.…”

Direct Involvement of Arachidonic Acid in the Development of Ear Edema via TRPV3

“…Conversely, when AA was applied to the mouse ear, the vascular permeability preceded the edemic response and neutrophil influx. Furthermore, TPA induced longer lasting edema associated with marked influx of neutrophils, whereas AA induced a short-lived edemic response with rapid onset associated with marked increases in the levels of oxidized fatty acids 29 . These pathways with some distinction between TPA and AA may reflect a biological difference such as the TRPV3 response.…”