Naslov
Effect of corticosteroids and chloroquine on monocyte TLR4 expression, signaling and cytokine production with implications for systemic lupus erythematosus

Autori
Cepika, Alma-Martina ; Morović Vergles, Jadranka ; Malenica, Branko ; Bendelja, Krešo ; Kapitanović, Sanja ; Gagro, Alenka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract Book, Godišnji sastanak Hrvatskog imunološkog društva 2009 / - , 2009

Skup
Godišnji sastanak Hrvatskog imunološkog društva 2009

Mjesto i datum
Starigrad, Hrvatska, 01.10.2009. - 04.10.2009

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
systemic lupus erythematosus; Toll-like receptors; TLR4; monocytes; NF-kappaB; cytokines; IL-6; TNF-alpha; corticosteroids; chloroquine
(systemic lupus erythematosus; Toll-like receptors; TLR4; monocytes; NF-kappaB; cytokines; IL-6 TNF-alpha; corticosteroids; chloroquine)

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

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