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 / - , 2010

Skup
The 7th International Congress on Autoimmunity

Mjesto i datum
Ljubljana, Slovenija, 05.05.2010. - 09.05.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
TLR4; SLE; NF-kappa B; TNF-alpha; IL-6

Sažetak
Aims: Early pathogen recognition and activation 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 are independent risk factors for infection, and bacteria prevail as dominant pathogens. Methods: 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. We also 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-AAD 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-a and IL-6 production, both via intracellular staining/flow cytometry and ELISA, in PBMC culture supernatants. Results: 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. Neither dexamethasone nor chloroquine suppressed LPS-induced NF-kappaB activation, although dexamethasone decreased TNF-a and IL-6 production. Conclusions: Therefore, even if low-dose steroids or chloroquine have no effect on TLR4 expression and signaling, steroids might decrease cytokine production during bacterial infection.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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