Effect of corticosteroids and chloroquine on monocyte TLR4 expression, signaling and cytokine production with implications for systemic lupus erythematosus (CROSBI ID 557004)
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Podaci o odgovornosti
Cepika, Alma-Martina ; Morović Vergles, Jadranka ; Malenica, Branko ; Bendelja, Krešo ; Kapitanović, Sanja ; Gagro, Alenka
engleski
Effect of corticosteroids and chloroquine on monocyte TLR4 expression, signaling and cytokine production with implications for systemic lupus erythematosus
Early pathogen recognition and adequate initiation of innate immunity is crucial in defense against infection. Systemic lupus erytematosus (SLE) is an autoimmune disease accompanied with reduced resistance to pathogens despite the overall hyperactivity of immune response. Immunosuppressive drugs (high-dose corticosteroids and cytotoxic agents) are independent risk factors for infection, and bacteria prevail as dominant pathogens. To explore whether milder imunomodulatory therapy (i.e. low-dose steroids, non-cytotoxic disease-modifying drugs) alters recognition and response to Gram-negative bacteria, we measured TLR4 expression in monocytes of SLE patients on chloroquine and/or low-dose steroid treatment, using whole-blood staining and flow cytometry. Additionally, we examined the drugs’ influence on monocyte TLR4 levels before and after 24- and 48h peripheral blood mononuclear cell (PBMC) culture with dexamethasone ± chloroquine. Viability was monitored with Annexin V/7-Aminoactinomycin D staining. To investigate the possible effect of treatment on TLR4 signal transduction, we measured LPS-induced NF-kappaB p65 subunit phosphorylation in monocytes using flow cytometry, after cultivating the PBMC as above. We also checked how drug exposure modulates LPS-induced monocyte TNF-alpha and IL-6 production, both via intracellular staining/flow cytometry and ELISA, in PBMC culture supernatants. SLE patients had lower frequency of TLR4+ monocytes than healthy controls. However, in vitro experiments suggested this is not the consequence of treatment, nor it correlates with disease activity. Moreover, neither dexamethasone nor chloroquine suppressed LPS-induced NF-kappaB activation, although dexamethasone decreased TNF-alpha and IL-6 production. Therefore, even if low-dose steroids or chloroquine don’t seem to affect TLR4 expression and signaling, steroids might decrease cytokine production during bacterial infection.
systemic lupus erythematosus; Toll-like receptors; TLR4; monocytes; NF-kappaB; cytokines; IL-6 TNF-alpha; corticosteroids; chloroquine
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Podaci o prilogu
2009.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
Godišnji sastanak Hrvatskog imunološkog društva 2009
predavanje
01.10.2009-04.10.2009
Starigrad, Hrvatska