Antiuveitis and Inhibition of Fibroblast-Like Corneal and Conjunctival Cell Cultures by Interleukin-1 Blockers, CK 125, CK 126 and CK 128

Xuan, Bo; Chiou, George C.Y.; Yamasaki, Tetsuo; Okawara, Tadashi

doi:10.1159/000055472

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…The recent discovery of synthetic IL-1 blockers which produce potent anti-inflammatory actions with few sideeffects, if any, is most exciting and warrants further studies [1,[4][5][6]. It has been found in this study that CK130 is the most potent anti-inflammatory agent of approximately 150 compounds investigated [1,[4][5][6][7][8][9][10][11].…”

Section: Resultsmentioning

confidence: 99%

“…Because of their anti-inflammatory actions, IL-1 blockers can also be used as inhibitors of fibroblast-like corneal and conjunctival cell proliferation [7][8][9][10][11][12]. If effective, these compounds could also be used to improve the success rate and functional period of cannula created after filtration surgery (trabeculectomy) in closeangle and low-tension glaucoma treatments [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

Xuan

Chiou

1998

Inflammopharmacol

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Effects of interleukin-1 (IL-1) blockers, CK130 and CK131, on IL-1-induced uveitis and proliferation of fibroblast-like corneal and conjunctival cells were investigated in this study. It was found that CK130 and CK131 inhibited IL-1-induced uveitis in rat eyes effectively at 3 mg/kg and 10 mg/kg, respectively. Further, CK130 and CK131 inhibited fibroblast-like corneal and conjunctival cell growth effectively at 10-300 microg/ml and 30-300 microg/ml, respectively. It was also found that DNA synthesis was markedly reduced by CK130 and CK131 at 30-100 microg/ml. RNA synthesis was also inhibited by these CK compounds but protein synthesis was little affected or enhanced.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

Xuan

Chiou

1998

Inflammopharmacol

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“…Numerous agents, including natural products and synthetic compounds, have been found to block IL-la-induced uveitis (23)(24)(25)(26)(27)(28)(29)(30)(31). These agents include tetrandrine (23), chalcone derivatives (24,25), osthole (26), and synthetic organic CK-compounds (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…These agents include tetrandrine (23), chalcone derivatives (24,25), osthole (26), and synthetic organic CK-compounds (27)(28)(29)(30)(31). Among the natural products, tetrandrine is the only one with acceptable safety, or least toxicity (23).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Interleukin-1α-Induced Uveitis and Inhibition of Fibroblast-like Cell Proliferation by Synthetic Interleukin-1 Blockers

Chiou¹,

Zhou²,

Xuan³

et al. 1999

Journal of Ocular Pharmacology and Therapeutics

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To treat uveitis and prolong the functional life of filtration surgery on glaucomatous eyes, some interleukin-1 (IL-1) blockers were used to inhibit IL-1-induced uveitis in rat eyes and to suppress proliferation of fibroblast-like corneal and conjunctival cells in the cell cultures, respectively. It was found in this research that the blood-aqueous barrier can be broken by IL-1alpha to allow fluorescein to enter the eyeballs and to be detected by fluorotron. The uveitis was effectively blocked by the IL-1 blockers studied in this research. It was also noted that the proliferation of fibroblast-like corneal and conjunctival cells was effectively inhibited by IL-1 blockers. The inhibition of cell growth seems to be caused primarily by the inhibition of RNA synthesis. There was a significant difference in the potency of IL-1 blockers to inhibit corneal vs. conjunctival cells. It was noted that conjunctival cells were more easily inhibited by IL-1 blockers than corneal cells. These results indicate that IL-1 blockers can suppress the proliferation of conjunctival cells at dose levels which do not affect the normal cell growth of corneal cells.

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Review: Effects of Nitric Oxide on Eye Diseases and Their Treatment

Chiou

2001

Journal of Ocular Pharmacology and Therapeutics

107

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Both underproduction and overproduction of nitric oxide (NO) could lead to various eye diseases. It is known that endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are activated in normal tissues to produce NO for physiological functions. Thus, underproduction of NO results in various eye diseases which could be corrected by providing NOS substrates or NO donors to lower the intraocular pressure, increase ocular blood flow, relax ciliary muscle, etc. On the other hand, immunological NOS (iNOS) is inducible only in pathological conditions by endotoxins, inflammation, and certain cytokines, such as interleukin-1 (IL-1), IL-6, TNF (tumor necrosis factor) and the like. Once induced, iNOS will produce large amounts of NO for long periods of time, so that NO is converted into NO2, nitrite, peroxynitrite and free radicals to induce pathophysiological actions, such as optic nerve degeneration and posterior retinal degeneration lesion, which lead to glaucoma, retinopathy, age-related macular degeneration (AMD), myopia, cataracts and uveitis. To treat/prevent these eye diseases, inhibitors of iNOS activity and/or iNOS induction could be tried.

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Antiuveitis and Inhibition of Fibroblast-Like Corneal and Conjunctival Cell Cultures by Interleukin-1 Blockers, CK 125, CK 126 and CK 128

Cited by 4 publications

References 11 publications

Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

Suppression of Interleukin-1α-Induced Uveitis and Inhibition of Fibroblast-like Cell Proliferation by Synthetic Interleukin-1 Blockers

Review: Effects of Nitric Oxide on Eye Diseases and Their Treatment

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