{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:35:01Z","timestamp":1773290101165,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T00:00:00Z","timestamp":1112832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIH-National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM-55005"],"award-info":[{"award-number":["GM-55005"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"NIH-National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM69861"],"award-info":[{"award-number":["GM69861"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucose-6-phosphate dehydrogenase (G6PD) supports cellular antioxidant pathways. G6PD deficiency is associated with malaria protection but was shown to worsen the clinical course to injury. This study tested whether G6PD deficiency manifests in altered cytokine responses using peritoneal macrophages from a G6PD-deficient mouse model with a degree of defect similar to the common type A\u2013 human G6PD deficiency. Lipopolysaccharide (LPS)-induced interleukin (IL)-10 and IL-12 production was doubled in G6PD-deficient macrophages compared with wild-type (WT). Protein kinase C (PKC) activation by phorbol-ester prior to LPS resulted in a fivefold greater IL-10 production in G6PD-deficient macrophages compared with WT. Interferon-\u03b3 treatment prior to LPS augmented IL-12 production in G6PD-deficient and WT macrophages and partially inhibited IL-10 production by G6PD-deficient macrophages. The antioxidants (N-acetyl-L-cysteine and glutathione ethyl-ester) blunted IL-10 and IL-12 production, indicating a role for oxidative stress in the observed response differences between deficient and WT macrophages. LPS-induced activation of nuclear factor-\u03baB, cyclic adenosine monophosphate response element-binding protein, and specificity protein 3 was augmented in G6PD-deficient cells compared with WT. The PKC\u03b4 inhibitor Rottlerin inhibited IL-10 and IL-12 production at different 50% effective-dose concentrations between deficient and WT macrophages, indicating elevated PKC\u03b4 activity in deficient cells. This study reveals that activated G6PD-deficient macrophages display an augmented production of cytokines with a prominent impact on IL-10 production. The altered cytokine responses are associated with augmented activation of redox-dependent transcription factors and PKC\u03b4. Alterations in signaling pathways and associated changes in cytokine production may play a role in modulating the inflammatory responses following bacterial or malarial infections in G6PD deficiency.<\/jats:p>","DOI":"10.1189\/jlb.0105010","type":"journal-article","created":{"date-parts":[[2005,4,8]],"date-time":"2005-04-08T00:33:52Z","timestamp":1112920432000},"page":"85-94","source":"Crossref","is-referenced-by-count":34,"title":["Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages"],"prefix":"10.1093","volume":"78","author":[{"given":"Jeanette","family":"Wilmanski","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School , Newark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School , Newark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin A","family":"Deitch","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School , Newark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Spolarics","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School , Newark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,4,7]]},"reference":[{"key":"2023033022483140900_","first-page":"3367","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Luzzatto","year":"1995"},{"key":"2023033022483140900_","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/jlb.63.5.534","article-title":"Endotoxemia, pentose cycle, and the oxidant\/antioxidant balance in the hepatic sinusoid","volume":"63","author":"Spolarics","year":"1998","journal-title":"J. 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