Lactobacillus rhamnosus could inhibit Porphyromonas gingivalis derived CXCL8 attenuation

ABSTRACT An increasing body of evidence suggests that the use of probiotic bacteria is a promising intervention approach for the treatment of inflammatory diseases with a polymicrobial etiology. P. gingivalis has been noted to have a different way of interacting with the innate immune response of the host compared to other pathogenic bacteria, which is a recognized feature that inhibits CXCL8 expression. Objective The aim of the study was to determine if P. gingivalis infection modulates the inflammatory response of gingival stromal stem cells (G-MSSCs), including the release of CXCL8, and the expression of TLRs and if immunomodulatory L. rhamnosus ATCC9595 could prevent CXCL8 inhibition in experimental inflammation. Material and Methods G-MSSCs were pretreated with L. rhamnosus ATCC9595 and then stimulated with P. gingivalis ATCC33277. CXCL8 and IL-10 levels were investigated with ELISA and the TLR-4 and 2 were determined through flow cytometer analysis. Results CXCL8 was suppressed by P. gingivalis and L. rhamnosus ATCC9595, whereas incubation with both strains did not abolish CXCL8. L. rhamnosus ATCC9595 scaled down the expression of TLR4 and induced TLR2 expression when exposed to P. gingivalis stimulation (p<0.01). Conclusions These findings provide evidence that L. rhamnosus ATCC9595 can modulate the inflammatory signals and could introduce P. gingivalis to immune systems by inducing CXCL8 secretion.

Chemokines and immunity / Quimiocinas e imunidade

Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family.

Quimiocinas são uma grande família de pequenas citocinas e seu peso molecular varia de 7 a 15kDa. As quimiocinas e seus receptores são capazes de controlar a migração e a residência de células imunes. Algumas quimiocinas são consideradas pró-inflamatórias e podem ser induzidas durante a resposta imune no sítio de infecção, enquanto outras são consideradas homeostáticas e estão envolvidas no controle da migração celular durante o desenvolvimento ou a manutenção dos tecidos. A importância fisiológica dessa família de mediadores é resultado de sua especificidade − os membros da família de quimiocinas induzem ao recrutamento de subtipos bem definidos de leucócitos. Existem duas grandes subfamílias de quimiocinas baseadas na posição dos resíduos de cisteínas: CXC e CC. Como regra geral, membros da família de quimiocinas CXC são quimiotáticos de neutrófilos, e as quimiocinas CC são quimiotáticos de monócitos e subtipos de linfócitos, apesar de existirem algumas exceções. Esta revisão discute o potencial papel das quimiocinas na inflamação focando nas duas quimiocinas mais bem caracterizadas: a proteína quimioatraente de monócitos-1, uma quimiocina CC, e a interleucina 8, uma quimiocina membro da subfamília CXC.

Effects of enteropathogenic bacteria & lactobacilli on chemokine secretion & Toll like receptor gene expression in two human colonic epithelial cell lines.

Background & objectives: The intestinal epithelium is part of the innate immune system responding to contact with pathogenic or commensal bacteria. The objective of this study was to compare innate responses of intestinal epithelial cell lines to pathogenic bacteria and to lactobacilli. Methods: Two human intestinal epithelial cell lines, HT29 (enterocyte-like) and T84 (crypt-like), were exposed to pathogenic bacteria representative of non invasive (Vibrio cholerae O1 and O139), adherent (enterohaemorrhagic Escherichia coli, EHEC) or invasive (Salmonella Typhimurium and Shigella flexneri) phenotypes and to non pathogenic Lactobacillus rhamnosus GG or Lactobacillus plantarum. Interleukin-8 (IL-8) was measured in culture supernatant by ELISA, while mRNA from cells was subjected to quantitative reverse transcriptase PCR for several other chemokines (CXCL1, CCL5 and CXCL5) and for Toll-like receptors (TLR) 2, 4, 5 and 9. Results: V. cholerae, S. Typhimurium, S. flexneri and EHEC induced IL-8 secretion from epithelial cells into the medium. Salmonella, Shigella and EHEC, but not V. cholerae, significantly increased mRNA expression of CXCL1. None of the pathogens induced CCL5 or CXCL5. Salmonella and Vibrio significantly increased TLR4 expression, while Vibrio and EHEC decreased TLR5 expression. EHEC also decreased TLR9 expression. Lactobacilli attenuated the IL-8 response of the cell lines to V. cholerae, Salmonella, and EHEC but did not significantly change the IL-8 response to Shigella. Interpretation & conclusions: Distinct patterns of epithelial cell chemokine responses were induced by the bacterial pathogens studied and these were modulated by commensal lactobacilli. Alterations in TLR expression by these pathogens are likely to be important in pathogenesis.

Pielonefritis, mecanismos patogénicos

La presencia de bacterias a nivel de la mucosa de las vías urinarias determina una respuesta inflamatoria. El factor responsable de la invasión de células inflamatorias es la IL6 (interleuquina 6) y los componentes bacterianos inductores son las adhesinas y el LPS de la membrana bacteriana. La actividad inflamatoria no es sólo responsable de los síntomas agudos sino de la eliminación bacteriana. En los estudios experimentales, los animales no reactivos al LPS fueron incapaces de eliminar las bacterias y en embarazadas se ha demostrado que una respuesta menor de IL6 puede relacionarse con la mayor incidencia de pielonefritis (1-4). La respuesta inflamatoria también ha sido relacionada con la producción de IL8 (interleuquina 8). Estudios en humanos han mostrado correlación entre concentración de IL8 urinaria y los recuentos leucocitarios (5).