Pseudomonas aeruginosa induces spatio-temporal secretion of IL-1β, TNFα, proMMP-9, and reduction of epithelial E-cadherin in human alveolar epithelial type II (A549) cells

  • Paulina Fuentes-Zacarias Department of Inmunobioquímica, Instituto Nacional de Perinatología “Isidro Espinoza de los Reyes” (INPerIER), Ciudad de México, México https://orcid.org/0000-0002-8335-9689
  • Diego Armando Arzate-Castañeda Department of Inmunobioquímica, Instituto Nacional de Perinatología “Isidro Espinoza de los Reyes” (INPerIER), Ciudad de México, México
  • Irma Sosa-González Department of Inmunología e Infectología, INPerIER, Ciudad de México, México
  • Graciela Villeda-Gabriel Department of Inmunología e Infectología, INPerIER, Ciudad de México, México
  • Iyari Morales-Méndez Department of Inmunobioquímica, Instituto Nacional de Perinatología “Isidro Espinoza de los Reyes” (INPerIER), Ciudad de México, México https://orcid.org/0000-0003-2582-9117
  • Mauricio Osorio-Caballero Department of Salud Sexual y Reproductiva, INPerIER, Ciudad de México, México
  • Addy Cecilia Helguera-Repetto Department of Inmunobioquímica, Instituto Nacional de Perinatología “Isidro Espinoza de los Reyes” (INPerIER), Ciudad de México, México
  • Fabián Nestor Díaz Department of Fisiología y Desarrollo Celular, INPerIER, Ciudad de México, México
  • Guadalupe García-López Department of Fisiología y Desarrollo Celular, INPerIER, Ciudad de México, México https://orcid.org/0000-0001-5751-8159
  • Oscar Flores-Herrera Department of Bioquimica, Escuela de Medicina, UNAM, Ciudad de México, México https://orcid.org/0000-0002-1034-9009
  • Francisco Arenas-Huertero Department of Patología Experimental, Hospital Infantil de México “Federico Gómez”, Ciudad de México, México
  • Carlos Eslava-Campos Laboratory of Patogenicidad Bacteriana, Unidad de Hemato-Oncología e Investigación, Hospital Infantil de México “Federico Gómez”, Ciudad de México, México https://orcid.org/0000-0001-7670-1960
  • Oscar Díaz-Ruíz Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Héctor Flores-Herrera Department of Inmunobioquímica, Instituto Nacional de Perinatología “Isidro Espinoza de los Reyes” (INPerIER), Ciudad de México, México https://orcid.org/0000-0002-7604-6158

Abstract

Pseudomonas aeruginosa, is an opportunistic bacterium with a high prevalence in diverse pulmonary infections. Although several genes are involved in the system of resistance and evasion of the immunological response of the host, little is known about the inflammatory, degradative, and cell-binding response induced by P. aeruginosa in human lung alveolar epithelial cells. The purpose of this study was to determine the cytokine expression (IL-1β and TNFα), pro matrix metalloproteinases activation (proMMP-2 and proMMP-9), and the effects on the cell-binding adhesion protein (E-cadherin) in an in vitro model of human lung alveolar epithelial cells. A549 cells were stimulated with a different number of colony-forming units of P. aeruginosa for 3, 6, and 24 hours. Subsequently, the culture medium was collected, IL-1β and TNFα levels were evaluated by ELISA; proMMP-2 and -9 levels were determined by substrate gel zymography, and the MMP-9 and E-cadherin assessed by immunostaining of A549 cells. Our results demonstrated that P. aeruginosa induces mainly the secretion of TNFα, increases actMMP-9 level, and significantly reduces the level of E-cadherin in the A549 cells. In summary, the inflammatory/degradative process induced by P. aeruginosa modulates the expression of the E-cadherin protein. The probable clinical implications of this study suggest the use of inhibitors that reduce the degradative activity of proMMP-9 which will be further explored in the next phase of this study.

Published
2021-05-04
Section
Articles