ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Vasoactive intestinal peptide downregulates proinflammatory TLRs while upregulating anti-inflammatory TLRs in the infected cornea.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Reparative Outcomes in Corneal Infection: Linking Adjunctive Tβ4 Treatment to Nerve Regeneration and Visual Function.Investigative ophthalmology & visual science · 2026Article
- Immunomodulatory Role of Neuropeptides in the Cornea.Biomedicines · 2022Review
- Mucosal immunology of the ocular surface.Mucosal immunology · 2022Review
- Osteopontin contributes to virus resistance associated with type I IFN expression, activation of downstream ifn-inducible effector genes, and CCR2Frontiers in immunology · 2022Article
- Targeting Inflammation Driven by HMGB1 in Bacterial Keratitis-A Review.Pathogens (Basel, Switzerland) · 2021Review
- Neuroanatomy and neurochemistry of rat cornea: Changes with age.The ocular surface · 2021Article
- The role of Th17 immunity in chronic ocular surface disorders.The ocular surface · 2021Review
- Corneal Allografts: Factors for and against Acceptance.Journal of immunology research · 2021Review
- Diabetic Corneal Neuropathy.Journal of clinical medicine · 2020Review
- Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy inInternational journal of molecular sciences · 2020Article
- Article
- A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases.International journal of molecular sciences · 2019Review
- Vasoactive Intestinal Peptide Deficiency Is Associated With Altered Gut Microbiota Communities in Male and Female C57BL/6 Mice.Frontiers in microbiology · 2019Article
- Negative regulators that mediate ocular immune privilege.Journal of leukocyte biology · 2018Review
- Tuning inflammation and immunity by the negative regulators IL-1R2 and IL-1R8.Immunological reviews · 2018Review
- Role of vasoactive intestinal peptide inInternational journal of ophthalmology · 2018Article
- Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent.Molecules (Basel, Switzerland) · 2017Article
- Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β.Cellular & molecular immunology · 2017Article
- Cytokine decoy and scavenger receptors as key regulators of immunity and inflammation.Cytokine · 2016Article
- Review of clinical and basic approaches of fungal keratitis.International journal of ophthalmology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
TLRs recognize microbial pathogens and trigger an immune response, but their regulation by neuropeptides, such as vasoactive intestinal peptide (VIP), during Pseudomonas aeruginosa corneal infection remains unexplored. Therefore, C57BL/6 (B6) mice were injected i.p. with VIP, and mRNA, protein, and immunostaining assays were performed. After VIP treatment, PCR array and real-time RT-PCR demonstrated that proinflammatory TLRs (conserved helix-loop-helix ubiquitous kinase, IRAK1, TLR1, TLR4, TLR6, TLR8, TLR9, and TNFR-associated factor 6) were downregulated, whereas anti-inflammatory TLRs (single Ig IL-1-related receptor [SIGIRR] and ST2) were upregulated. ELISA showed that VIP modestly downregulated phosphorylated inhibitor of NF-κB kinase subunit α but upregulated ST2 ~2-fold. SIGIRR was also upregulated, whereas TLR4 immunostaining was reduced in cornea; all confirmed the mRNA data. To determine whether VIP effects were cAMP dependent, mice were injected with small interfering RNA for type 7 adenylate cyclase (AC7), with or without VIP treatment. After silencing AC7, changes in mRNA levels of TLR1, TNFR-associated factor 6, and ST2 were seen and unchanged with addition of VIP, indicating that their regulation was cAMP dependent. In contrast, changes were seen in mRNA levels of conserved helix-loop-helix ubiquitous kinase, IRAK1, 2, TLR4, 9 and SIGIRR following AC7 silencing alone; these were modified by VIP addition, indicating their cAMP independence. In vitro studies assessed the effects of VIP on TLR regulation in macrophages and Langerhans cells. VIP downregulated mRNA expression of proinflammatory TLRs while upregulating anti-inflammatory TLRs in both cell types. Collectively, the data provide evidence that VIP downregulates proinflammatory TLRs and upregulates anti-inflammatory TLRs and that this regulation is both cAMP dependent and independent and involves immune cell types found in the infected cornea.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.