Epithelial-Immune Cell Crosstalk Determines the Activation of Immune Cells In Vitro by the Human Cathelicidin LL-37 at Low Physiological Concentrations.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, 2011-
    • Subject Terms:
      Cathelicidins*/pharmacology ; Epithelial Cells*; Humans ; Antimicrobial Cationic Peptides/pharmacology ; Caco-2 Cells ; Cytokines ; Signal Transduction
    • Abstract:
      The only human cathelicidin, LL-37, is a host defense antimicrobial peptide with antimicrobial activities against protozoans, fungi, Gram(+) and Gram(-) bacteria, and enveloped viruses. It has been shown in experiments in vitro that LL-37 is able to induce the production of various inflammatory and anti-inflammatory cytokines and chemokines by different human cell types. However, it remains an open question whether such cytokine induction is physiologically relevant, as LL-37 exhibited its immunomodulatory properties at concentrations that are much higher (>20 μg/mL) than those observed in non-inflamed tissues (1-5 μg/mL). In the current study, we assessed the permeability of LL-37 across the Caco-2 polarized monolayer and showed that this peptide could pass through the Caco-2 monolayer with low efficiency, which predetermined its low absorption in the gut. We showed that LL-37 at low physiological concentrations (<5 μg/mL) was not able to directly activate monocytes. However, in the presence of polarized epithelial monolayers, LL-37 is able to activate monocytes through the MAPK/ERK signaling pathway and induce the production of cytokines, as assessed by a multiplex assay at the protein level. We have demonstrated that LL-37 is able to fulfill its immunomodulatory action in vivo in non-inflamed tissues at low physiological concentrations. In the present work, we revealed a key role of epithelial-immune cell crosstalk in the implementation of immunomodulatory functions of the human cathelicidin LL-37, which might shed light on its physiological action in vivo.
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    • Contributed Indexing:
      Keywords: Caco-2 cells; LL-37; cytokines; epithelial immunity; host defense peptide; human cathelicidin; immunomodulatory action; xMAP
    • Accession Number:
      0 (Antimicrobial Cationic Peptides)
      0 (Cathelicidins)
      0 (Cytokines)
      0 (CAMP protein, human)
    • Publication Date:
      Date Created: 20230928 Date Completed: 20231005 Latest Revision: 20231005
    • Publication Date:
      20231215
    • Accession Number:
      PMC10526274
    • Accession Number:
      10.3390/biom13091316
    • Accession Number:
      37759716