Endotoxin-induced production of inflammatory mediators by cultured ciliary epithelial cells

Helbig, Horst; Kittredge, Karen L.; Gurley, Rebecca C.; Thurau, Stephan; Palestine, Alan G.; Nussenblatt, Robert B.

doi:10.3109/02713689008999616

Cited by 16 publications

(6 citation statements)

References 13 publications

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“…Both PGI 2 and PGE 2 increased significantly in vascular endothelial cells in response to LPS or TNF-␣ (27), in ciliary epithelial cells in response to LPS (28), in gingival fibroblasts in response to IL-1 or TNF-␣ (29), and in myometrial cells in response to IL-1 or TNF-␣ (30). Similarly, PGI 2 and PGE 2 production by aortic endothelial cells was elevated in response to xenoreactive antibodies and complement (31).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prostaglandin E2

Brock

McNish

Peters‐Golden

1999

Journal of Biological Chemistry

277

184

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The two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, both metabolize arachidonic acid to prostaglandin H 2 , which is subsequently processed by downstream enzymes to the various prostanoids. In the present study, we asked if the two isoforms differ in the profile of prostanoids that ultimately arise from their action on arachidonic acid. Resident peritoneal macrophages contained only cyclooxygenase-1 and synthesized (from either endogenous or exogenous arachidonic acid) a balance of four major prostanoids: prostacyclin, thromboxane A 2 , prostaglandin D 2 , and 12-hydroxyheptadecatrienoic acid. Prostaglandin E 2 was a minor fifth product, although these cells efficiently converted exogenous prostaglandin H 2 to prostaglandin E 2 . By contrast, induction of cyclooxygenase-2 with lipopolysaccharide resulted in the preferential production of prostacyclin and prostaglandin E 2 . This shift in product profile was accentuated if cyclooxygenase-1 was permanently inactivated with aspirin before cyclooxygenase-2 induction. The conversion of exogenous prostaglandin H 2 to prostaglandin E 2 was only modestly increased by lipopolysaccharide treatment. Thus, cyclooxygenase-2 induction leads to a shift in arachidonic acid metabolism from the production of several prostanoids with diverse effects as mediated by cyclooxygenase-1 to the preferential synthesis of two prostanoids, prostacyclin and prostaglandin E 2 , which evoke common effects at the cellular level. Prostaglandins (PGs)1 are a family of intercellular and intracellular messengers derived from arachidonic acid (AA). These mediators exert a wide range of effects on processes such as smooth muscle tone, vascular permeability, cellular proliferation, and inflammatory/immune function. In many cases, different PGs will have opposing actions. For example, PGD 2 and thromboxane (TxA 2 ) cause smooth muscle contraction, whereas PGE 2 and prostacyclin (PGI 2 ) cause relaxation (reviewed in Refs. 1-4). Similarly, TxA 2 increases, but PGI 2 inhibits, platelet aggregation. The net effect evoked by PGs may, ultimately, depend on the balance of these opposing forces.The initial step in the synthesis of PGs from AA is mediated by cyclooxygenase (COX, also known as prostaglandin H synthase or prostaglandin endoperoxide synthase), of which two isoforms are recognized (reviewed in Refs. 2-4). COX-1 is expressed constitutively in most cell types, and prostanoids derived from COX-1 are thought to be important in gastric and renal homeostasis. COX-2, on the other hand, is the product of an immediate early gene and is rapidly expressed only after exposure of cells to hormones, mitogenic stimuli, and inflammatory mediators, like bacterial lipopolysaccharide (LPS). The induction of COX-2, with the resultant production of prostanoids, can contribute to parturition, inflammation, pain, fever, and certain types of cancer. The ability of aspirin to permanently inactivate both COX isoforms indiscriminately explains both its analgesic and anti-inflammatory properties, through ...

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Section: Discussionmentioning

confidence: 99%

Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prostaglandin E2

Brock

McNish

Peters‐Golden

1999

Journal of Biological Chemistry

277

184

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“…Jackson et al and Jung et al reported that IL-1β induced the expression of VEGF mRNA and protein in rheumatoid synoviocytes [27] and human lung epithelial cells [28]. Soluble or membranebound forms of IL-1β were produced by several cell types within the eye, including Mueller cells, macrophages, and vascular endothelial cells [29,30]. In fact, high levels of locally-produced IL-1β and VEGF have been found in mouse retinas undergoing retinal degeneration [31], as well as in the vitreous humor of patients with proliferative diabetic retinopathy [16,32], suggesting that the inflammatory milieu might enhance VEGF production.…”

Section: Discussionmentioning

confidence: 99%

The effect of clonidine on VEGF expression in human retinal pigment epithelial cells (ARPE-19)

Watanabe

Zhang

Kitagawa

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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“…COX-2 is responsible for the production of great amount of pro-inflammatory PGs at inflammatory sites in animals and human with inflammatory diseases [ 19 ]. ICB is one of the major sources of NO and PGE2 production as well as inflammatory cells and plays a key role in the pathogenesis of EIU [ 8 , 9 ]. Our results show that the luteolin attenuated the expression of iNOS and COX-2 in the ICB, suggesting that blocking the expression of iNOS and COX-2 is one of the anti-inflammatory mechanisms of luteolin.…”

Section: Discussionmentioning

confidence: 99%

Luteolin attenuates endotoxin-induced uveitis in Lewis rats

Kanai

Hatta

Nagata

et al. 2016

The Journal of Veterinary Medical Science

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The aim of the present study was to investigate the efficacy of luteolin on endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injections of lipopolysaccharide (LPS). One hr before the LPS injection, 0.1, 1 or 10 mg/kg luteolin or 1 mg/kg prednisolone was intraperitoneally injected. We investigated its effect upon clinical scores, cellular infiltration and protein leakage, as well as on the level of tumor necrosis factor (TNF)-α, nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor (AqH). Histologic examination and immunohistochemical analysis in the iris-ciliary body (ICB) were performed to determine the expressions of cyclooxygenase (COX)-2 and inducible NO synthase (iNOS), and then the activated nuclear factor (NF)-κB p65, I kappa B (IκB)-α degradation, phosphorylated (p)-IκB kinase (IKK) α/β and activator protein (AP)-1 c-Jun. Luteolin suppressed, in a dose-dependent manner, the clinical scores, number of inflammatory cells, the protein concentration, and the TNF-α, NO and PGE2 levels in the AqH and improved the histiologic status of the ocular tissue. Luteolin suppressed the expression of iNOS and COX-2 and the activated NF-κB p65, IκB-α degradation, p-IKKα/β and AP-1 p-c-Jun in the ICB. The anti-inflammatory potency of 10 mg/kg luteolin was as strong as that observed with 1 mg/kg prednisolone. These results demonstrate that luteolin attenuates ocular inflammation by inhibiting expression and release of inflammatory markers, along with the inhibition of the activated NF-κB pathway and at least partly AP-1 activity in the ICB.

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Endotoxin-induced production of inflammatory mediators by cultured ciliary epithelial cells

Cited by 16 publications

References 13 publications

Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prostaglandin E2

Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prostaglandin E2

The effect of clonidine on VEGF expression in human retinal pigment epithelial cells (ARPE-19)

Luteolin attenuates endotoxin-induced uveitis in Lewis rats

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