PMID- 33194837
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 10
DP  - 2020
TI  - Exoantigens of Paracoccidioides spp. Promote Proliferation and Modulation of 
      Human and Mouse Pulmonary Fibroblasts.
PG  - 590025
LID - 10.3389/fcimb.2020.590025 [doi]
LID - 590025
AB  - Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection caused 
      by thermally dimorphic fungi of the genus Paracoccidioides. Endemic in Latin 
      America, PCM presents with high incidence in Brazil, Colombia, and Venezuela, 
      especially among rural workers. The main clinical types are acute/subacute (AF) 
      form and chronic form (CF). Even after effective antifungal treatment, patients 
      with CF usually present sequelae, such as pulmonary fibrosis. In general, 
      pulmonary fibrosis is associated with dysregulation wound healing and abnormal 
      fibroblast activation. Although fibrogenesis is recognized as an early process in 
      PCM, its mechanisms remain unknown. In the current study, we addressed the role 
      of Paracoccidioides spp. exoantigens in pulmonary fibroblast proliferation and 
      responsiveness. Human pulmonary fibroblasts (MRC-5) and pulmonary fibroblasts 
      isolated from BALB/c mice were cultivated with 2.5, 5, 10, 100, and 250 microg/ml of 
      exoantigens produced from P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, 
      Pb8334, and Pb66) isolates. Purified gp43, the immunodominant protein of P. 
      brasiliensis exoantigens, was also evaluated at concentrations of 5 and 10 microg/ml. 
      After 24 h, proliferation and production of cytokines and growth factors by 
      pulmonary fibroblasts were evaluated. Each exoantigen concentration promoted a 
      different level of interference of the pulmonary fibroblasts. In general, 
      exoantigens induced significant proliferation of both murine and human pulmonary 
      fibroblasts (p < 0.05). All concentrations of exoantigens promoted decreased 
      levels of IL-6 (p < 0.05) and VEGF (p < 0.05) in murine fibroblasts. 
      Interestingly, decreased levels of bFGF (p < 0.05) and increased levels of TGF-beta1 
      (p < 0.05) and pro-collagen I (p < 0.05) were observed in human fibroblasts. The 
      gp43 protein induced increased TGF-beta1 production by human cells (p = 0.02). In 
      conclusion, our findings showed for the first time that components of P. 
      brasiliensis and P. lutzii interfered in fibrogenesis by directly acting on the 
      biology of pulmonary fibroblasts.
CI  - Copyright (c) 2020 Almeida Donanzam, Donato, Reis, Silva, Finato, Santos, 
      Cavalcante, Mendes and Venturini.
FAU - Almeida Donanzam, Debora de Fatima
AU  - Almeida Donanzam DF
AD  - Faculdade de Medicina, Universidade Federal do Mato Grosso do Sul, Campo Grande, 
      Brazil.
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Donato, Tatiani Ayako Goto
AU  - Donato TAG
AD  - Faculdade de Ciencias, UNESP, Bauru, Brazil.
FAU - Dos Reis, Karoline Haghata
AU  - Dos Reis KH
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - da Silva, Adriely Primo
AU  - da Silva AP
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Finato, Angela Carolina
AU  - Finato AC
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Dos Santos, Amanda Ribeiro
AU  - Dos Santos AR
AD  - Faculdade de Medicina, Universidade Federal do Mato Grosso do Sul, Campo Grande, 
      Brazil.
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Cavalcante, Ricardo Souza
AU  - Cavalcante RS
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Mendes, Rinaldo Poncio
AU  - Mendes RP
AD  - Faculdade de Medicina, Universidade Federal do Mato Grosso do Sul, Campo Grande, 
      Brazil.
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
FAU - Venturini, James
AU  - Venturini J
AD  - Faculdade de Medicina, Universidade Federal do Mato Grosso do Sul, Campo Grande, 
      Brazil.
AD  - Faculdade de Medicina, Departamento de Doencas Tropicais e Diagnostico por 
      Imagem, UNESP, Botucatu, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201030
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Antigens, Fungal)
SB  - IM
MH  - Animals
MH  - Antigens, Fungal
MH  - Brazil
MH  - Cell Proliferation
MH  - Colombia
MH  - Fibroblasts
MH  - Humans
MH  - Latin America
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Paracoccidioides
MH  - *Paracoccidioidomycosis
PMC - PMC7662685
OTO - NOTNLM
OT  - cell response
OT  - growth factors
OT  - paracoccidioidomycosis
OT  - pulmonary fibroblast
OT  - pulmonary fibrosis
EDAT- 2020/11/17 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/01/01
CRDT- 2020/11/16 08:53
PHST- 2020/07/31 00:00 [received]
PHST- 2020/10/07 00:00 [accepted]
PHST- 2020/11/16 08:53 [entrez]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2020.590025 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2020 Oct 30;10:590025. doi: 
      10.3389/fcimb.2020.590025. eCollection 2020.