Regulation of TLR expression, a new perspective for the role of VIP in immunity

Gomariz, Rosa P.; Arranz, Alicia; Juarranz, Yasmina; Gutiérrez‐Cañas, Irene; García-Gómez, María; Leceta, Javier; Martı́nez, Carmen

doi:10.1016/j.peptides.2007.07.005

Cited by 33 publications

(28 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of VIP-mediated immunomodulation is believed to stem from the fact that VIP can induce regulatory T-cells (Treg) and that it creates an environment that favors the differentiation of Type 2 T-helper cells (Th2) that mainly produce interleukin (IL)-4 and IL-10 cells over Th1-cells which produce IFN- γ and Th17-cells which produce IL-17 (5,6,11,14–19). This change of environment induces the anti-inflammatory activity in the context of the Th1/Th17 dominated T-cell response that is seen in most of the organ-specific chronic inflammatory diseases (5,6,11,14–19).…”

Section: Introductionmentioning

confidence: 99%

Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

et al. 2012

View full text Add to dashboard Cite

Purpose To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP). Methods VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined. Results Both formulations significantly extend in vivo residence time compared to unformulated VIP. Formulation toxicity is dependent on loading percentage, showing major differences between the two carrier types. Both formulations increase in vivo potency of unformulated VIP and show acute MTDs at least 140 times lower than unformulated VIP, but still at least 100 times higher than the anticipated highest human dose, 1–5 μg/kg. These nanocarriers prevented a significant drop in arterial blood pressure compared to unformulated VIP. Conclusions While both carriers enhance in vivo residence time compared to unformulated VIP and reduce the drop in blood pressure immediately after injection, PGC is the excipient of choice to extend residence time and improve the safety of potent therapeutic peptides such as VIP.

show abstract

Section: Introductionmentioning

confidence: 99%

Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

et al. 2012

View full text Add to dashboard Cite

show abstract

“…LPS present in the outer membranes of some Gram-negative pathogens such as ETEC triggers the production of proinflammatory mediators that may contribute to intestinal inflammation and damage during the infection [67]. The modulation of TLR expression is one of the most recent functions in immunity attribute to VIP [68]–[70]. The current results showed that ETEC K88 infection increased the expression of TLR2, TLR4 and MyD88, and induced the phosphorylation of IKBα), p-ERK, p-JNK and p38.…”

Section: Discussionmentioning

confidence: 99%

Modulatory Effects of Vasoactive Intestinal Peptide on Intestinal Mucosal Immunity and Microbial Community of Weaned Piglets Challenged by an Enterotoxigenic Escherichia coli (K88)

Wang

Sun

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Toll-like receptors (TLRs) recognize microbial pathogens and trigger immune response, but their regulation by neuropeptide-vasoactive intestinal peptide (VIP) in weaned piglets infected by enterotoxigenic Escherichia coli (ETEC) K88 remains unexplored. Therefore, the study was conducted to investigate its role using a model of early weaned piglets infected by ETEC K88. Male Duroc×Landrace×Yorkshire piglets (n = 24) were randomly divided into control, ETEC K88, VIP, and ETEC K88+VIP groups. On the first three days, ETEC K88 and ETEC K88+VIP groups were orally administrated with ETEC K88, other two groups were given sterile medium. Then each piglet from VIP and ETEC K88+VIP group received 10 nmol VIP intraperitoneally (i.p.) once daily, on day four and six. On the seventh day, the piglets were sacrificed. The results indicated that administration of VIP improved the growth performance, reduced diarrhea incidence of ETEC K88 challenged pigs, and mitigated the histopathological changes of intestine. Serum levels of IL-2, IL-6, IL-12p40, IFN-γ and TNF-α in the ETEC K88+ VIP group were significantly reduced compared with those in the ETEC group. VIP significantly increased IL-4, IL-10, TGF-β and S-IgA production compared with the ETEC K88 group. Besides, VIP could inhibit the expression of TLR2, TLR4, MyD88, NF-κB p65 and the phosphorylation of IκB-α, p-ERK, p-JNK, and p-38 induced by ETEC K88. Moreover, VIP could upregulate the expression of occludin in the ileum mucosa compared with the ETEC K88 group. Colon and caecum content bacterial richness and diversity were lower for pigs in the ETEC group than the unchallenged groups. These results demonstrate that VIP is beneficial for the maturation of the intestinal mucosal immune system and elicited local immunomodulatory activities. The TLR2/4-MyD88 mediated NF-κB and MAPK signaling pathway may be critical to the mechanism underlying the modulatory effect of VIP on intestinal mucosal immune function and bacterial community.

show abstract

“…TLR6 functions through the formation of heterodimer with its family member and typically forms heterodimer with TLR2 in responding to stimulation by bacterial antigen. 21 We next analyzed whether co-expression of TLR6 and TLR2 could enhance BCL10 or API2-MALT1-mediated NF-kB activation in the presence of LPS stimulation. As expected, TLR6/2 co-expression, in the presence of LPS stimulation, were synergistic with BCL10 and API2-MALT1 in activating the NF-kB pathway (Figure 4).…”

Section: Tlr6 Expression Enhances Nf-kb Activation By Bcl10 and Api2-mentioning

confidence: 99%

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Hamoudi

Appert

et al. 2010

Leukemia

View full text Add to dashboard Cite

Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/ BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-jB pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-jB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-jB target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/lymphoma (BCL)2, while translocationnegative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-jB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.

show abstract

Regulation of TLR expression, a new perspective for the role of VIP in immunity

Cited by 33 publications

References 63 publications

Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

Modulatory Effects of Vasoactive Intestinal Peptide on Intestinal Mucosal Immunity and Microbial Community of Weaned Piglets Challenged by an Enterotoxigenic Escherichia coli (K88)

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Contact Info

Product

Resources

About