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Role of protein kinase C in cytokine secretion by lung epithelial cells during infection with Paracoccidioides brasiliensis.

ABSTRACT: In this study, we investigated the role of protein kinases C (PKCs) in interleukin (IL)-6 and IL-8 secretion by human lung epithelial A549 cells during infection with the fungal pathogen Paracoccidioides brasiliensis. Rottlerin and the broad spectrum PKC inhibitor Go 6983 reduced cytokine levels in A549 cell-P. brasiliensis cultures. Next, by western blot, we verified that infection with this fungus led to phosphorylation of PKC ? (Thr(505)). By using a peptide inhibitor for PKC ? or PKC ? short interfering RNA technique, IL-6 and IL-8 levels in A549-P. brasiliensis cultures were also reduced. Together, these results indicate that P. brasiliensis promotes IL-6 and IL-8 secretion by A549 cells in a PKC ?-dependent manner.

SUBMITTER: Alcantara C

PROVIDER: S-EPMC4626587 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Role of protein kinase C in cytokine secretion by lung epithelial cells during infection with Paracoccidioides brasiliensis.

Alcantara Cristiane C Maza Paloma Korehisa PK Barros Bianca Carla Silva Campitelli BC Suzuki Erika E

Pathogens and disease 20150706 7

In this study, we investigated the role of protein kinases C (PKCs) in interleukin (IL)-6 and IL-8 secretion by human lung epithelial A549 cells during infection with the fungal pathogen Paracoccidioides brasiliensis. Rottlerin and the broad spectrum PKC inhibitor Go 6983 reduced cytokine levels in A549 cell-P. brasiliensis cultures. Next, by western blot, we verified that infection with this fungus led to phosphorylation of PKC δ (Thr(505)). By using a peptide inhibitor for PKC δ or PKC δ short ...[more]

PMID: 26152710

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Project description:BackgroundParacoccidioidomycosis (PCM) is one of the most important systemic mycoses in Latin America and the leading fungal cause of mortality in non-immunosuppressed individuals in Brazil. However, HIV/PCM co-infection can increase the clinical severity in these co-infected patients. This co-infection is rarely reported in the literature mainly because of the different epidemiological profiles of these infections. Furthermore, PCM is a neglected and non-notifiable disease, which may underestimate the real importance of this disease. The advent of molecular studies on the species of the genus Paracoccidioides has expanded the knowledge regarding the severity and the clinical spectrum in PCM. In this context, the development of studies to describe the association of the Paracoccidioides phylogenetic cryptic species in vulnerable populations, such as HIV-infected patients, appears relevant.ObjectiveTo describe the clinical, epidemiological, therapeutic and prognostic aspects in HIV/PCM co-infected patients, along with the molecular identification of the Paracoccidioides species involved in these cases.MethodsThe investigators performed a molecular and clinical retrospective study involving HIV/PCM co-infected patients, from a reference centre for PCM care in the endemic area of Rio de Janeiro, Brazil, from 1998 to 2015. Molecular identification of the fungal strains was done by amplification of partial sequences of arf and gp43 genes.FindingsOf 89 patients diagnosed with PCM by fungal isolation in the culture, a viable isolate was recovered for molecular analysis from 44 patients. Of these 44 patients, 28 (63.6%) had their serum samples submitted for enzyme immunoassay tests for screening of HIV antibodies, and 5 (17.9%) had a positive result. All cases were considered severe, with a variable clinical presentation, including mixed, acute/subacute clinical forms and a high rate of complications, requiring combination therapy. Paracoccidioides brasiliensis S1 was the species identified in all cases.ConclusionsHIV/PCM co-infection can change the natural history of this fungal disease. The authors reinforce the need to include HIV screening diagnostic tests routinely for patients with PCM.

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Role of protein kinase C in cytokine secretion by lung epithelial cells during infection with Paracoccidioides brasiliensis.

Publications

Role of protein kinase C in cytokine secretion by lung epithelial cells during infection with Paracoccidioides brasiliensis.

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