Role of porin of Shigella dysenteriae type 1 in modulation of lipopolysaccharide mediated nitric oxide and interleukin-1 release by murine peritoneal macrophages

Abstract

The ability of Shigella dysenteriae type 1 porin to induce the release of nitric oxide (NO) and interleukin-1 (IL-1) from peritoneal macrophages of mouse and to regulate lipopolysaccharide (LPS) and gamma interferon (IFN-gamma) mediated release of the two proinflammatory mediators was investigated. Porin released nitrite when added to macrophage cultures. A maximum of 3.2-fold nitrite release by macrophages was observed with 100 ng ml(-1) of porin. The nitrite release of LPS was enhanced significantly by lower concentrations of porin, whereas the effect of IFN-gamma was enhanced by porin at higher concentrations. Polysaccharide (PS) moiety of LPS stimulated the nitrite release of elicited macrophages by 1.6-fold compared to untreated control. It also enhanced the stimulatory effect of 1 and 10 ng ml(-1) of porin by 1.3-fold. Lipid A (LPA) moiety of LPS did not release nitrite, nor did it increase the porin mediated nitrite production. Porin treated 24 h old macrophage culture supernatants were applied for ConA activated thymocyte proliferation as a measure for determination of IL-1 release. Sixty percent depletion of thymocyte proliferation was observed when the porin treated macrophage supernatants were absorbed with anti-IL-1 antibody. A maximum of 5.5-fold increase of thymocyte proliferation over control was found with 1 and 10 ng ml(-1) of porin. One or 10 ng ml(-1) of porin and LPS augmented the thymocyte growth, 1.5-fold beyond that obtained by porin and 1.8-/1. 7-fold more than that obtained by LPS, alone. Similarly, porin and IFN-gamma co-stimulated the cell growth also. PS enhanced the thymocyte proliferation by 5-fold. It also enhanced the thymocyte growth by co-stimulating 1.4-fold the effect observed by 1 or 10 ng ml(-1) of porin alone. LPA could not participate in the cell proliferating activity nor did it enhance the stimulatory effect of porin. Therefore, both nitrite release and thymocyte proliferation by LPS could be substituted by PS only. The tight association of the two bacterial outer membrane components, porin and LPS, could be a necessary co-signal for boosting the release of the two proinflammatory mediators, namely NO and IL-1, which may be associated with the inflammatory response of the colon during Shigella invasion.

Vibrio cholerae porin OmpU mediates M1-polarization of macrophages/monocytes via TLR1/TLR2 activation

“…It has been shown in various studies, that porins are involved in the bacterial adherence processes and in the induction of apoptosis of the host cells (Bernardini et al, 1993;Muller et al, 1999;Negm and Pistole, 1999). Roles of porins in inducing pro-inflammatory responses, and their underlying signaling processes have been established in various reports (Biancone et al, 1997;Biswas, 2000;Galdiero et al, 2001;Gupta et al, 1999;Sakharwade et al, 2013;Sakharwade et al, 2015). Due to its immuno-modulatory property, porins are thought to be the potential vaccine candidate (Latz et al, 2004;Tabaraie et al, 1994).…”

Outer membrane proteins analysis of Shigella sonnei and evaluation of their antigenicity in Shigella infected individuals

“…Besides that, the OMPs due to their location, have been known to elicit a host immune response and are also categorized as virulence factors [ 14 ]. Some proteins in OMPs of the bacterium are exposed on the cell surface and may influence the physiological functions of the tissue, contributing to the mechanisms of pathogenicity and development of inflammatory response [ 15 , 16 ].…”

Shigella flexneri 3a Outer Membrane Protein C Epitope Is Recognized by Human Umbilical Cord Sera and Associated with Protective Activity

“…Alternatively, the use of outer membrane proteins (OMP) was proposed. The OMPs markedly contribute to the mechanisms of pathogenicity, progression of the infection, and to the development of the inflammatory response [14]–[15]. These proteins are part of the cell envelope of Gram-negative bacteria and participate in maintaining cell integrity, pathogen adaptation to the environment and interaction with the host cells [16]–[17].…”