{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:05:47Z","timestamp":1767211547932},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3999,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The activation of neutrophils with particulate stimuli such as zymosan induces the generation of the C\u2010X\u2010C chemokine interleukin (IL)\u20108. There is evidence that neutrophil derived IL\u20108 plays an important role in human diseases such as the adult respiratory distress syndrome. In the present study, we examined the effects of cyclic AMP elevating agents on the ability of human neutrophils to generate IL\u20108 in response to zymosan particles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The PDE4 inhibitor rolipram had limited effect on zymosan\u2010induced IL\u20108 generation. In contrast, the PDE4 inhibitors RP 73401 and SB 207499 concentration\u2010dependently suppressed IL\u20108 generation. The potency of these inhibitors was RP 73401 &gt; SB 207499 &gt; rolipram which is correlated with their rank order of potency at inhibiting the catalytic site of purified neutrophil PDE4. Pretreatment of neutrophils with the PDE3 inhibitor ORG 9935 or the PDE5 inhibitor zaprinast had no effect on IL\u20108 generation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The prostanoids prostaglandin E<jats:sub>1<\/jats:sub> (PGE<jats:sub>1<\/jats:sub>) and PGE<jats:sub>2<\/jats:sub> inhibited zymosan\u2010induced IL\u20108 release from neutrophils in a dose\u2010dependent manner, in response to 10<jats:sup>\u22125<\/jats:sup><jats:sc>M<\/jats:sc> PGE<jats:sub>1<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> inhibiting IL\u20108 generation by 89% and 75%, respectively. Similarly, the \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonist salbutamol also inhibited IL\u20108 generation, but it was less effective than the prostanoids.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Significant synergism between prostanoids or salbutamol and the PDE4 inhibitors to inhibit IL\u20108 generation was observed. In contrast, there was no significant synergism between PGE<jats:sub>2<\/jats:sub> and the PDE3 inhibitor ORG 9935 or the PDE5 inhibitor zaprinast.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In order to evaluate the potential role of protein kinase A in mediating the inhibitory effects of cyclic AMP\u2010elevating agents, we used the protein kinase A inhibitors, H 89 and KT 5720. Pretreatment of neutrophils with these drugs completely reversed the inhibitory effects of a combination treatment with rolipram and PGE<jats:sub>2<\/jats:sub> on zymosan\u2010induced IL\u20108 release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Microscopic examination revealed that most neutrophils contained one or more zymosan particles and that combination treatment with rolipram and PGE<jats:sub>2<\/jats:sub> noticeably reduced the number of ingested particles. Moreover, there was a significant reduction in the percentage of neutrophils which ingested three or more zymosan particles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thus, our results demonstrate that cyclic AMP\u2010elevating agents modulate the ability of neutrophils to generate IL\u20108 in response to a particulate stimulus. However, these agents also modulate the ability of neutrophils to phagocytose zymosan particles. Whether this effect will translate into inhibition of the ability of neutrophils to deal with infectious agents needs to be investigated further.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 1260\u20131266; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701723\">10.1038\/sj.bjp.0701723<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701723","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:25:05Z","timestamp":1106940305000},"page":"1260-1266","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Effect of PDE4 inhibitors on zymosan\u2010induced IL\u20108 release from human neutrophils: synergism with prostanoids and salbutamol"],"prefix":"10.1111","volume":"123","author":[{"given":"B\u2010 T.","family":"Au","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M M.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P D.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.4049\/jimmunol.152.11.5411","article-title":"Zymosan\u2010induced interleukin\u20108 release from human neutrophils involves activation via the Cd11b\/CD18 receptor and endogenous platelet activating factor as an autocrine modulator","volume":"152","author":"Au B\u2010T.","year":"1994","journal-title":"J. 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