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Effects of rolipram, a selective inhibitor of type 4 phosphodiesterase, on lipopolysaccharide-induced uveitis in rats.
Invest Ophthalmol Vis Sci 2004; 45(8):2497-502IO

Abstract

PURPOSE

To investigate effects of rolipram, an inhibitor of type 4 phosphodiesterase, on lipopolysaccharide (LPS)-induced uveitis in Wistar rats.

METHODS

A total of 100 microg LPS was injected into the rat footpad. Rolipram (Wako Pure Chemical, Osaka, Japan) was injected intraperitoneally 30 minutes before administration of LPS. Levels of intracameral protein, cells, E-selectin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and nitrite were determined. E-selectin, TNF-alpha, IL-6, and inducible nitric oxide synthase (iNOS) mRNAs and immunohistochemical reactivity of nuclear factor (NF)-kappa B and TNF-alpha were also examined in the iris-ciliary body.

RESULTS

After LPS injection, intracameral protein and cells increased from 18 to 30 hours later. Rolipram, however, inhibited elevation of protein and cells. After LPS injection, mRNA levels of E-selectin, TNF-alpha, and IL-6 in the iris-ciliary body increased 3 hours later, and iNOS mRNA increased 6 hours later. Elevation of mRNA levels for E-selectin, TNF-alpha, and IL-6 was inhibited by rolipram. After LPS injection, intracameral TNF-alpha and IL-6 levels increased 4 to 6 hours later, and nitrite levels increased 14 to 20 hours later. Elevation of TNF-alpha and IL-6 levels was decreased by rolipram. Rolipram did not affect iNOS mRNA and nitrite levels. Immunoreactivity of NF-kappa B was strong 1 hour after LPS injection, and was decreased by rolipram. Immunoreactivity of TNF-alpha was strong 4 hours after LPS injection and was decreased by rolipram.

CONCLUSIONS

NF-kappa B translocation and expression of E-selectin, TNF-alpha, and IL-6 are involved in the pathogenesis of LPS-induced uveitis and are inhibited by rolipram. The inhibitory effect of rolipram in uveitis may be independent of iNOS synthesis.

Authors+Show Affiliations

Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan. ophthal@ms.toyama-mpu.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15277469

Citation

Chi, Zai-Long, et al. "Effects of Rolipram, a Selective Inhibitor of Type 4 Phosphodiesterase, On Lipopolysaccharide-induced Uveitis in Rats." Investigative Ophthalmology & Visual Science, vol. 45, no. 8, 2004, pp. 2497-502.
Chi ZL, Hayasaka S, Zhang XY, et al. Effects of rolipram, a selective inhibitor of type 4 phosphodiesterase, on lipopolysaccharide-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2004;45(8):2497-502.
Chi, Z. L., Hayasaka, S., Zhang, X. Y., Hayasaka, Y., & Cui, H. S. (2004). Effects of rolipram, a selective inhibitor of type 4 phosphodiesterase, on lipopolysaccharide-induced uveitis in rats. Investigative Ophthalmology & Visual Science, 45(8), pp. 2497-502.
Chi ZL, et al. Effects of Rolipram, a Selective Inhibitor of Type 4 Phosphodiesterase, On Lipopolysaccharide-induced Uveitis in Rats. Invest Ophthalmol Vis Sci. 2004;45(8):2497-502. PubMed PMID: 15277469.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of rolipram, a selective inhibitor of type 4 phosphodiesterase, on lipopolysaccharide-induced uveitis in rats. AU - Chi,Zai-Long, AU - Hayasaka,Seiji, AU - Zhang,Xue-Yun, AU - Hayasaka,Yoriko, AU - Cui,Hu-Shan, PY - 2004/7/28/pubmed PY - 2004/9/1/medline PY - 2004/7/28/entrez SP - 2497 EP - 502 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 45 IS - 8 N2 - PURPOSE: To investigate effects of rolipram, an inhibitor of type 4 phosphodiesterase, on lipopolysaccharide (LPS)-induced uveitis in Wistar rats. METHODS: A total of 100 microg LPS was injected into the rat footpad. Rolipram (Wako Pure Chemical, Osaka, Japan) was injected intraperitoneally 30 minutes before administration of LPS. Levels of intracameral protein, cells, E-selectin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and nitrite were determined. E-selectin, TNF-alpha, IL-6, and inducible nitric oxide synthase (iNOS) mRNAs and immunohistochemical reactivity of nuclear factor (NF)-kappa B and TNF-alpha were also examined in the iris-ciliary body. RESULTS: After LPS injection, intracameral protein and cells increased from 18 to 30 hours later. Rolipram, however, inhibited elevation of protein and cells. After LPS injection, mRNA levels of E-selectin, TNF-alpha, and IL-6 in the iris-ciliary body increased 3 hours later, and iNOS mRNA increased 6 hours later. Elevation of mRNA levels for E-selectin, TNF-alpha, and IL-6 was inhibited by rolipram. After LPS injection, intracameral TNF-alpha and IL-6 levels increased 4 to 6 hours later, and nitrite levels increased 14 to 20 hours later. Elevation of TNF-alpha and IL-6 levels was decreased by rolipram. Rolipram did not affect iNOS mRNA and nitrite levels. Immunoreactivity of NF-kappa B was strong 1 hour after LPS injection, and was decreased by rolipram. Immunoreactivity of TNF-alpha was strong 4 hours after LPS injection and was decreased by rolipram. CONCLUSIONS: NF-kappa B translocation and expression of E-selectin, TNF-alpha, and IL-6 are involved in the pathogenesis of LPS-induced uveitis and are inhibited by rolipram. The inhibitory effect of rolipram in uveitis may be independent of iNOS synthesis. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/15277469/Effects_of_rolipram_a_selective_inhibitor_of_type_4_phosphodiesterase_on_lipopolysaccharide_induced_uveitis_in_rats_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.03-1373 DB - PRIME DP - Unbound Medicine ER -