Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB from<i>Porphyromonas gingivalis</i>

Zhang, Ping; Martin, Michael; Yang, Qiu-Bo; Michalek, Suzanne M.; Katz, Jannet

doi:10.1128/iai.72.2.637-644.2004

Cited by 36 publications

(34 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hence, reduced expression of HLA-DR on AM is linked with a hypo-activation state [33] and may promote immune tolerance [34,35]. Moreover, CD80 plays an important role in providing costimulatory signals required for the development of antigenspecific immune responses [36]. Thus, the reduced expression of HLA-DR and CD80 found in AM of COPD patients suggests that the cell-mediated immune function of AM may be abnormal in these patients.…”

Section: Discussionmentioning

confidence: 96%

Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD

Pons¹

2005

Eur Respir J

View full text Add to dashboard Cite

Alveolar macrophages (AM) participate actively in the inflammatory response that characterises chronic obstructive pulmonary disease (COPD). The present study investigated potential changes in AM phenotypes in patients with COPD.Using flow cytometry, the surface expression of receptors implicated in phagocytosis (CD44, CD36, CD51, CD61, CD14), antigen-presenting capacity (human leukocyte antigen (HLA)-DR), costimulatory molecules (CD80, CD86, CD40) and complement receptor type 3 were assessed in AM from 18 patients with COPD, 14 smokers with normal lung function and nine nonsmokers.When compared to smokers with normal lung function and nonsmokers, the surface expression of HLA-DR and CD80 was lower in AM of patients with COPD. In addition, these patients had a higher percentage of AM with a low level surface expression of CD44. There did not appear to be any difference in the other receptors studied in AM between the three groups. The expression of all these receptors in peripheral blood monocytes also did not differ between groups.In conclusion, these observations suggest that the cell-mediated immune function of alveolar macrophages can be reduced in chronic obstructive pulmonary disease, and that this is a local rather than a systemic event.

show abstract

Section: Discussionmentioning

confidence: 96%

Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD

Pons¹

2005

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Because prostacyclin selectively upregulates CD86 but not CD80 on B cells, after Tcell-B cell interactions, the resulting T cell differentiation may be favored toward Th2 type. Several groups demonstrated the dominant role for CD86 in Th2 activation and differentiation (2,3). In other words, FDCs regulate T cell differentiation indirectly by controlling the APC potential of B cells in the GC.…”

Section: Discussionmentioning

confidence: 99%

Beraprost Enhances the APC Function of B Cells by Upregulating CD86 Expression Levels

Kim

Park

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Lipid mediators are emerging as important regulators of the immune system. Based on our previous result that shows strong expression of prostacyclin synthase in the germinal center, we investigated whether prostacyclin would regulate the APC function of B cells. Owing to the very short half-life of prostacyclin in experimental conditions, we used a more stable analog, beraprost. Beraprost increased the amounts of the costimulatory molecule CD86 but not CD80 on the surface of activated B cells in time- and dose-dependent manners. However, the enhancing effect of beraprost was not observed on memory B cells, centroblasts, and centrocytes. Beraprost required BCR and CD40 signals to upregulate CD86 expression levels. Other prostanoids such as PGE2, 6-keto-PGF1α, and PGF2α failed to alter CD86 expression levels, whereas other prostacyclin analogs were as potent as beraprost. Results carried out with receptor antagonists revealed that beraprost enhanced CD86 levels by binding to prostacyclin receptor IP and by increasing intracellular cAMP concentrations. Beraprost-treated B cells potently stimulated allogeneic T cells, which was significantly abolished by CD86 neutralization. Our data imply an unrecognized cellular and molecular mechanism about the germinal center reactions.

show abstract

“…Studies have shown that rHagB induces the production of a mixed Th1-and Th2-like cytokine pattern, as determined by the production of IFN-␥, IL-2, IL-4, and IL-10 by rat splenic lymphoid cells (19) or by the production of IL-4, IL-5, and IFN-␥ by mouse CD4 ϩ T cells (40). In the present study, rHagB was found to induce mRNA expression and protein production by mouse peritoneal macrophages of other proinflammatory cytokines, i.e., TNF-␣ and IL-12 p40, as well as IFN-␥ and the anti-inflammatory cytokine IL-10.…”

Section: Discussionmentioning

confidence: 99%

“…rHagB was purified as previously described (38,40). Briefly, rHagB was purified from the soluble fraction of lysates of Escherichia coli JM 109 expressing the hagB gene by using a His-bind resin column, according to the manufacturer's instruction (Novagen, Madison, Wis.).…”

Section: Methodsmentioning

confidence: 99%

“…This finding supports the potential use of rHagB as an antigen for the development of a vaccine against adult periodontitis. Furthermore, we have shown a critical role of B7 costimulatory molecules for the preferential differentiation of T-helper cells for responses to rHagB (40). However, the signaling pathways and regulatory molecules involved in host immune responses to HagB have not been delineated.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

Zhang¹,

Martin²,

Michalek

et al. 2005

Infect Immun

Self Cite

View full text Add to dashboard Cite

Hemagglutinin B (HagB) is a nonfimbrial adhesin expressed on the surface of Porphyromonas gingivalis and has been implicated as a potential virulence factor involved in mediating the attachment of the bacteria to host cells. However, the molecular mechanisms underlying host responses to HagB and their roles in pathogenesis have yet to be elucidated. Mitogen-activated protein kinases (MAPKs) are activated following engagement of a variety of cell surface receptors via dual tyrosine and threonine phosphorylation and are thought to be involved in various cellular responses. The purpose of this study was to determine the role of intracellular signaling pathways including the MAPKs and NF-B in regulating the production of proinflammatory and anti-inflammatory cytokines following stimulation of murine macrophages with recombinant HagB (rHagB). Stimulation of peritoneal macrophages with rHagB resulted in the production of the proinflammatory cytokines interleukin-12p40 (IL-12p40), gamma interferon (IFN-␥), and tumor necrosis factor alpha, as well as the anti-inflammatory cytokine IL-10. We also demonstrated the activation of extracellular signal-related kinase (ERK), c-Jun NH 2 -terminal protein kinase (JNK), and p38 MAPKs by rHagB-stimulated macrophages. Furthermore, blocking of the ERK and p38 signaling pathways by using specific inhibitors revealed differential regulatory roles in the rHagB-mediated production of proinflammatory and anti-inflammatory cytokines. ERK and p38 were important in down-regulation of IL-12p40 and IFN-␥ production and up-regulation of IL-10 production. The enhanced levels of IL-12p40 in rHagB-stimulated macrophages by inhibition of ERK or p38 activity were partially attributable to the inhibition of IL-10 production. Moreover, NF-B was found to be critical for up-regulation of IL-12p40 and down-regulation of IL-10 production in rHagB-stimulated macrophages. Taken together, our results demonstrate a role for the p38 and ERK pathways and the transcription factor NF-B in modulating key immunoregulatory cytokines involved in the development of immune responses to P. gingivalis HagB.

show abstract

Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB fromPorphyromonas gingivalis

Cited by 36 publications

References 45 publications

Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD

Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD

Beraprost Enhances the APC Function of B Cells by Upregulating CD86 Expression Levels

Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B

Contact Info

Product

Resources

About