The immunomodulatory functions of prolactin (PRL) are well recognized. Augmented PRL plasma levels were observed in patients with advanced tuberculosis (TB). Recently, we have reported that LPS and Mycobacterium bovis (M. bovis) induced differential expression of PRL receptor (PRLR) isoforms in THP-1 cells and bovine macrophages, respectively. The aim of this work was to determine whether PRL should be considered as a potential modulator of the signaling pathways and cytokine synthesis, induced by culture filtrate protein (CFP) from M. bovis in THP-1 monocytes. The THP-1 cells were stimulated with PRL (20ng/mL), M. bovis CFP (50μg/mL). PRLR as well as phosphorylated STAT3, STAT5, Akt1/2/3, ERK1/2 and p38 expression were evaluated by Western blot. IL1-β, TNF-α, IL-6, IL-12, IL-8, and IL-10 concentrations were measured by ELISA. Our results demonstrated that the expression pattern of PRLR short isoforms is induced by M. bovis CFP. M bovis CFP induced phosphorylation of Akt2, ERK1/2, p38, STAT3, and STAT5 pathways. In turn, PRL only activated the JAK2/STAT3-5 signaling pathway. However, when combined both stimuli, PRL significantly increased STAT3-5 phosphorylation and downregulated Akt2, ERK1/2, and p38 phosphorylation. As expected, M. bovis CFP induced substantial amounts of IL1-β, IL-6, TNF-α, IL-8, IL-12, and IL-10. However, the PRL costimulation considerably decreased IL1-β, TNF-α, and IL-12 secretion, and increased IL-10 production. This results suggest that up-regulation of IL-10 by PRL might be modulating the pro-inflammatory response against mycobacterial antigens through the MAPK pathway.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2014.08.006DOI Listing

Publication Analysis

Top Keywords

bovis cfp
16
erk1/2 p38
12
prl
9
induced culture
8
culture filtrate
8
bovis
8
thp-1 cells
8
cfp bovis
8
stat3 stat5
8
il1-β tnf-α
8

Similar Publications

Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis.

Res Vet Sci

December 2024

Instituto Nacional de Tecnología Agropecuaria, Instituto de Agrobiotecnología y Biología Molecular (IB-IABiMo), UEDD INTA-CONICET, Hurlingham, Buenos Aires, Argentina; CONICET, Argentina. Electronic address:

Bovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen.

View Article and Find Full Text PDF

Mycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination.

Tuberculosis (Edinb)

December 2024

Instituto de Agrobiotecnología y Biología Molecular, (IABIMO) INTA-CONICET, Argentina; Instituto de Biotecnología, CICVyA, Instituto Nacional de Tecnología Agropecuaria N. Repetto and De los Reseros, Hurlingham, 1686, Buenos Aires, Argentina. Electronic address:

A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile.

View Article and Find Full Text PDF

Development and evaluation of a triplex droplet digital PCR method for differentiation of , and BCG.

Front Microbiol

June 2024

National Animal Tuberculosis Reference Laboratory, Division of Zoonoses Surveillance, China Animal Health and Epidemiology Center, Qingdao, Shandong, China.

Article Synopsis
  • Tuberculosis caused by Mycobacterium tuberculosis complex (MTBC) remains a major global health issue, emphasizing the need for effective detection methods to differentiate its main pathogens.
  • The study introduces a new testing method called triplex droplet digital polymerase chain reaction (ddPCR), which uses different probe fluorophores to accurately target genes associated with three pathogens: MTBC, its variants, and BCG.
  • The results show that triplex ddPCR is more sensitive and specific than current methods, detecting lower levels of pathogens in various sample types (including milk, tissue, and swabs) with high repeatability and without cross-reaction to other organisms.
View Article and Find Full Text PDF

The Esx-1 family proteins of the Type VII secretion systems of and have been assessed and are frequently used as candidates for tuberculosis (TB) diagnosis in both humans and animals. The presence of ESAT-6 and CFP 10 proteins, which are the most immunogenic proteins of the Esx-1 system and have been widely investigated for the immunodiagnosis of tuberculosis, in some and in , poses limitations for their use in specific diagnoses of TB. As such, to improve the specificity of the ESAT-6/CFP 10-based cell-mediated immunity (CMI) assays, other proteins encoded by genes within and outside the RD 1 region of the esx-1 locus have been evaluated as candidate antigens for CMI, as well as to investigate humoral responses in combination with ESAT-6 and or CFP 10, with varying specificity and sensitivity results.

View Article and Find Full Text PDF

BCG vaccination is increasingly reconsidered in the effective prevention of bovine tuberculosis (bTB). However, the primary challenge in BCG vaccination for cattle is the lack of a technique for differentiating between infected and vaccinated animals (DIVA). This study aimed to establish a novel DIVA diagnostic test based on an interferon-gamma in vitro release assay (IGRA).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!