title: mRNA expression of alpha and beta isoforms of glucocorticoid receptor in peripheral blood mononuclear cells of patients with tuberculosis and its relation with components of the immunoendocrine response.
abstract: We have analyzed the expression of glucocorticoid receptor (GR) isoforms by real time RT-qPCR in PBMCs from 19 controls (HCo) and 28 TB patients (8 mild; 12 moderate; 8 severe), HIV(-) and similar sex and age distribution. mRNA hGRα/β ratios were found higher in TB patients respect to those in HCo. However, when analyzing for disease severity such overall trend was at the expense of mild and moderate patients, with severe cases showing a lower mRNA hGRα/β ratio with respect to the other patient groups. This suggested some degree of resistance to endogenous glucocorticoids in patients with severe TB, since hGRαα dimer mediates the biological functions of GC, with the GRβ isoform acting as an inhibitor of GC activity. Levels of IL-6, IL-18, IFN-γ and Cortisol were significantly increased in severe and moderate cases, whereas DHEA values were found decreased in them (p<0.05 respect to HCo). Analysis on the relationship between plasma levels of these immuno-endocrine mediators with the mRNA expression of hGRα and hGRβ showed that IL-6 was positively associated with hGRα in mild TB patients (p<0.01), whereas a negative correlation between IFN-γ and hGRβ was observed in severe cases (p<0.01). As regard to hormones, DHEA was positively associated with hGRα in moderate and severe cases (p<0.01). This group also showed a negative correlation between hGRα and Cortisol/DHEA ratios (p<0.05). Changes in the systemic levels of cytokine and adrenal hormones are likely to affect GR expression in a differential fashion and according to the amount of pulmonary involvement.
authors.affiliation: Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, 2000 Rosario, Argentina.
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Attilio
authors.forename: Luciano
authors.initials: L
authors.lastname: D'Attlio
authors.forename: Ernesto
authors.initials: E
authors.lastname: Trini
authors.forename: Bettina
authors.initials: B
authors.lastname: Bongiovanni
authors.forename: Griselda
authors.initials: G
authors.lastname: Dídoli
authors.forename: Walter
authors.initials: W
authors.lastname: Gardeñez
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Nannini
authors.forename: Adriana
authors.initials: A
authors.lastname: Giri
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Bottasso
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Bay
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone