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Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection.
Int J Mol Sci 2019; 20(18)IJ

Abstract

BACKGROUND

HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis.

OBJECTIVE

To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors.

METHODS

PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified.

RESULTS

Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load.

CONCLUSION

Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.

Authors+Show Affiliations

Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA. Medellín 050010, Colombia. geronimoferia23@gmail.com.Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA. Medellín 050010, Colombia. maria.rugeles@udea.edu.co.Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA. Medellín 050010, Colombia. juankhernandez@gmail.com. Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín 050016, Colombia. juankhernandez@gmail.com.Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA. Medellín 050010, Colombia. lujanarmy@gmail.com.Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA. Medellín 050010, Colombia. nataliataborda@gmail.com. Grupo de Investigaciones Biomédicas Uniremington, Programa de Medicina, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, Medellín 050016, Colombia. nataliataborda@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31514274

Citation

Feria-Garzón, Manuel G., et al. "Sulfasalazine as an Immunomodulator of the Inflammatory Process During HIV-1 Infection." International Journal of Molecular Sciences, vol. 20, no. 18, 2019.
Feria-Garzón MG, Rugeles MT, Hernandez JC, et al. Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection. Int J Mol Sci. 2019;20(18).
Feria-Garzón, M. G., Rugeles, M. T., Hernandez, J. C., Lujan, J. A., & Taborda, N. A. (2019). Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection. International Journal of Molecular Sciences, 20(18), doi:10.3390/ijms20184476.
Feria-Garzón MG, et al. Sulfasalazine as an Immunomodulator of the Inflammatory Process During HIV-1 Infection. Int J Mol Sci. 2019 Sep 11;20(18) PubMed PMID: 31514274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection. AU - Feria-Garzón,Manuel G, AU - Rugeles,María T, AU - Hernandez,Juan C, AU - Lujan,Jorge A, AU - Taborda,Natalia A, Y1 - 2019/09/11/ PY - 2019/06/26/received PY - 2019/09/04/revised PY - 2019/09/06/accepted PY - 2019/9/14/entrez KW - HIV KW - inflammasomes KW - inflammation KW - sulfasalazine KW - toll-like receptors JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 18 N2 - BACKGROUND: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. OBJECTIVE: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. METHODS: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified. RESULTS: Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load. CONCLUSION: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31514274/Sulfasalazine_as_an_Immunomodulator_of_the_Inflammatory_Process_during_HIV-1_Infection L2 - http://www.mdpi.com/resolver?pii=ijms20184476 DB - PRIME DP - Unbound Medicine ER -