The relationship between host defens peptides an adrena steroids . An account of reciprocal influences

DÍAZ, ARIANA; DIAB, MAGDALENA; MATA-ESPINOZA, DULCE; BINI, ESTELA ISABEL; D'ATTILIO, LUCIANO; BOTTASSO, OSCAR; HERNÁNDEZ-PANDO, ROGELIO; BAY, MARÍA LUISA; BONGIOVANNI, BETTINA

CYTOKINE.

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2023

1043-4666

a crucial role in the immune response against mycobacteria. Given our former studies in tuberculosis patientswherein their plasma levels of such peptides correlated with steroid hormone concentrations, we now studiedthe reciprocal influence of cortisol and/or dehydroepiandrosterone (DHEA) on HDPs biosynthesis and LL-37 onadrenal steroidogenesis.Main methods: Cultures of macrophages derived from the THP-1 line were treated with cortisol (10-6M) and/orDHEA (10-6M and 10-7M) and stimulated with irradiated M. tuberculosis (Mi) or infected M. tuberculosis strainH37Rv to assess cytokine production, HDPs, reactive oxygen species (ROS) and colony forming units. Culturesof NCI-H295-R adrenal line were treated with LL37 (5, 10, and 15 μg/ml) for 24 h to further measure cortisoland DHEA levels together with steroidogenic enzyme transcripts.Key findings: In macrophages, M. tuberculosis produced an increase of IL-1β, TNFα, IL-6, IL-10, LL-37, HBD-2,and HBD-3 levels, irrespective of DHEA treatment. Adding cortisol to M. tuberculosis-stimulated cultures (withor without DHEA) decreased the amounts of these mediators, compared to only stimulated cultures. AlthoughM. tuberculosis reduced ROS levels, DHEA increased these values in addition to diminishing intracellular mycobacterialgrowth (no matter cortisol treatment).In turn, studies on adrenal cells showed that LL-37 reduced the production of cortisol and DHEA besides modifyingtranscripts for some steroidogenic enzymes.Significance: while adrenal steroids seem to influence the production of HDPs, the former compounds are alsolikely to modulate adrenal biogenesis.