Calcium triggers β‐defensin (hBD‐2 and hBD‐3) and chemokine macrophage inflammatory protein‐3α (MIP‐3α/CCL20) expression in monolayers of activated human keratinocytes

Pernet, Ingrid; Reymermier, C.; Guezennec, Anne; Branka, Jean-Eric; Guesnet, J.; Perrier, Éric; Dezutter‐Dambuyant, Colette; Schmitt, Daniel; Viac, J.

doi:10.1111/j.0906-6705.2003.00086.x

Cited by 48 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We and others have previously shown that FnCW induces TNF-␣ and IL-1␤ transcript expression in HOECs (41,62), and these two cytokines have been shown to induce CCL20 release from several epithelial cell lines (8,49,51). Here, we looked to see if these cytokines could induce the release of CCL20 from HOECs.…”

Section: Ccl20 Release Requires Rapid De Novo Generation and Is Inhibmentioning

confidence: 91%

Fusobacterium nucleatum and Human Beta-Defensins Modulate the Release of Antimicrobial Chemokine CCL20/Macrophage Inflammatory Protein 3α

et al. 2011

View full text Add to dashboard Cite

Cells of the innate immune system regulate immune responses through the production of antimicrobial peptides, chemokines, and cytokines, including human beta-defensins (hBDs) and CCL20. In this study, we examined the kinetics of primary human oral epithelial cell (HOEC) production of CCL20 and hBDs in response to Fusobacterium nucleatum, a commensal bacterium of the oral cavity, which we previously showed promotes HOEC induction of hBDs. HOECs secrete maximal levels of CCL20 at 6 h, following stimulation by F. nucleatum cell wall (FnCW). The kinetics of CCL20 release is distinct from that of hBD-2 and -3, which peaks after 24 h and 48 h of FnCW stimulation, respectively. FnCW-induced release of CCL20 by HOECs requires both transcriptional and translational activation. Release of CCL20 by HOECs is inhibited by brefeldin A, suggesting that it is secreted through a vesicle transport pathway. Other epithelium-derived agents that FnCW induces, such as hBD-2, hBD-3, tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤), are also able to release CCL20. By focusing on mitogen-activated protein kinases, we show that both extracellular signalregulated kinase 1/2 and p38, but not JNK, are required for hBD-, TNF-␣-, and IL-1␤-induced secretion of CCL20 by HOECs. The ability of FnCW and its induced hBDs to produce proinflammatory cytokines and CCL20 suggests the broad role of F. nucleatum and human antimicrobial peptides in primary immune responses elicited by oral epithelium.

show abstract

Section: Ccl20 Release Requires Rapid De Novo Generation and Is Inhibmentioning

confidence: 91%

Fusobacterium nucleatum and Human Beta-Defensins Modulate the Release of Antimicrobial Chemokine CCL20/Macrophage Inflammatory Protein 3α

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The recruitment of immature DCs and memory T cells by hBD-2 and hBD-3 is mediated through the G i -protein-coupled receptor (GiPCR) CCR6 [35,147,[149][150][151]. The competition between hBD-2 and MIP-3α (the chemokine ligand of CCR6) for CCR6 also was recently confirmed for stimulated keratinocytes [152]. Combined, these results not only confirm common signaling pathways in β-defensins and MIP-3α regulation, but also suggest an important and complementary role of β-defensins in innate and adaptive immunity.…”

Section: Chemotactic Effects and In Vivo Immunoenhancing Activitymentioning

confidence: 99%

Human β-defensins

Pazgier

Hoover

Yang

et al. 2006

Cell. Mol. Life Sci.

454

418

View full text Add to dashboard Cite

The last decade led to the discovery and characterization of several human beta-defensins. Analysis of genomic information indicates that the number of beta-defensin-like molecules encoded by the human genome may number in the tens. Growing interest in beta-defensins steadily enhances our knowledge about various aspects of their gene location, expression patterns and the transcription factors involved in their regulation in vivo. The hallmark property of beta-defensins, their antimicrobial activity, is clearly only the tip of the iceberg in the extensive network of inter-relations within the immune system in which these peptides function. Structural studies of beta-defensins provide the molecular basis for a better understanding of their properties, functions and their potential for practical applications. In this review, we present some recent advances in the studies of human beta-defensins, with an emphasis on possible correlations between their structural and functional properties.

show abstract

“…HBD-2-induction in skin keratinocytes only occurs in differentiated cells. Whereas basal cell layers of the epidermis and a basal cell carcinoma cell line (KB) always lack hBD-2-immunoreactivity [66], in cultured primary keratinocytes conditions that facilitate differentiation -such as culture of keratinocytes in the presence of high concentrations of Ca 2+ -increases background hBD-2 expression [108,109], suggesting that sufficient differentiation is a prerequisite of hBD-2 production in skin. Genomic analyses of the hBD-2 promoter region revealed several putative transcription factor binding sites, including nuclear factor kappa B (NFkB), activator protein 1 (AP-1), AP-2 und NF-IL-6, which are known to be involved in the induction and regulation of inflammatory responses [60,110].…”

Section: Hbd-2 Is Induced By Differentiation Il-1 and P Aeruginosamentioning

confidence: 99%

Antimicrobial skin peptides and proteins

Schröder

Harder

2006

Cell. Mol. Life Sci.

223

216

View full text Add to dashboard Cite

Human skin is permanently exposed to microorganisms, but rarely infected. One reason for this natural resistance might be the existence of a 'chemical barrier' consisting in constitutively and inducibly produced antimicrobial peptides and proteins (AMPs). Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Apart from being expressed in vivo in inflammatory lesions, some AMPs are also focally expressed in skin in the absence of inflammation. This suggests that non-inflammatory stimuli of endogenous and/or exogenous origin can also stimulate AMP synthesis without inflammation. Such mediators might be ideal 'immune stimulants' to induce only the innate antimicrobial skin effector molecules without causing inflammation.

show abstract

Calcium triggers β‐defensin (hBD‐2 and hBD‐3) and chemokine macrophage inflammatory protein‐3α (MIP‐3α/CCL20) expression in monolayers of activated human keratinocytes

Cited by 48 publications

References 23 publications

Fusobacterium nucleatum and Human Beta-Defensins Modulate the Release of Antimicrobial Chemokine CCL20/Macrophage Inflammatory Protein 3α

Fusobacterium nucleatum and Human Beta-Defensins Modulate the Release of Antimicrobial Chemokine CCL20/Macrophage Inflammatory Protein 3α

Human β-defensins

Antimicrobial skin peptides and proteins

Contact Info

Product

Resources

About