Mast Cells Are Key Mediators of Cathelicidin-Initiated Skin Inflammation in Rosacea

Muto, Yumiko; Wang, Zhenping; Vanderberghe, Matthieu; Two, Aimee M.; Gallo, Richard L.; Nardo, Anna Di

doi:10.1038/jid.2014.222

Cited by 163 publications

(147 citation statements)

References 28 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…[7,8] Furthermore, the number of MCs is increased in skin lesions of patients with rosacea, and inhibition of this increased MC activity has been suggested as a potential treatment for rosacea. [9] Interestingly, we found an increase in mRnA levels of chymase and tryptase in the MCs in mouse skin injected with LL-37, which was consistent with previous study by Muto et al [4] In addition, Muto et al suggested that MCs play an important role in the development of rosacea by demonstrating that MC stabilizers improve rosacea phenotype by decreasing MMP activity and MC proteases (chymase and tryptase) in both rosacea-induced mouse model and patients with rosacea. [4] In our study, we showed that treatment with brimonidine significantly decreased the expression of these enzymes compared with the LL-37 group, demonstrating that the vasoconstrictor activity of brimonidine in human skin vessels is of potential direct relevance to the treatment of erythema in rosacea.…”

Section: Resultssupporting

confidence: 91%

“…It is presumed that vasoconstriction caused by brimonidine may reduce the recruitment of immune cells such as MCs, which play an important role in the development of rosacea, to the skin. [1,4] To our knowledge, we first confirmed that the number of MCs and mRnA levels of MC proteases were reduced by brimonidine gel in rosacea-like mouse skin and suggested that the therapeutic action of brimonidine may include inhibition of MCs.…”

Section: Resultsmentioning

confidence: 55%

“…This result is consistent with reports that increased MCs were observed in rosacea skin with elevated levels of cathelicidin LL-37 peptide. [4,5] To investigate the effect of the brimonidine gel on MC infiltration, we analysed the expression of the MC markers such as tryptase and chymase using RT-PCR. Chymase and tryptase are serine proteases that are abundant in MCs and are used as essential markers of MC activity.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of mast cell infiltration in an LL‐37‐induced rosacea mouse model using topical brimonidine tartrate 0.33% gel

Kim

Jeong

et al. 2017

Experimental Dermatology

View full text Add to dashboard Cite

Brimonidine is a highly selective α2-adrenergic receptor agonist approved by the FDA for the treatment of rosacea. Rosacea is a major clinical disease with vasodilatation and rash on the centre of the face, and that brimonidine as a vasoconstrictor can act as a remedy for rosacea. However, there is no study of how brimonidine has an effect on rosacea-related immune cells or mechanisms in the skin to improve rosacea. In this study, we observed that clinical features of rosacea induced by LL-37 in Balb/c mice were improved after the application of brimonidine gel, and we also showed a marked decrease in the number of inflammatory cells, especially mast cells (MCs) histologically. Furthermore, we confirmed that mRnA levels of MC enzymes increased by LL-37 were reduced by brimonidine gel. To our knowledge, we first found that brimonidine has a mechanism of treating rosacea by reducing the number and mRnA levels of MC-specific enzymes, an important immune cell in the pathogenesis of rosacea. | BACKGROUNDRosacea is a common chronic inflammatory skin disease characterized by telangiectasia and flushing.[1] The erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity in the central part of the face. Brimonidine tartrate 0.33% gel (Mirvaso gel; Galderma, Lausanne, Switzerland), a highly selective α2-adrenergic receptor agonist, was recently recommended for the treatment of persistent facial erythema in patients with rosacea due to its potent vasoconstrictive effects. [2] Several clinical studies have demonstrated that brimonidine rapidly improves facial flushing and erythema. [2,3] However, the molecular and histological effects of brimonidine on rosacea remain largely unknown. Although the vasoconstrictive property of brimonidine gel has been suggested to contribute to the therapeutic effect, it was assumed that not only contracting the expanded blood vessels would act on the therapeutic mechanism. | QUESTION ADDRESSEDThe aims of this study were to investigate the histological changes and gene expression levels in rosacea-like skin lesions when applied with brimonidine and to identify the role of brimonidine gel in the pathogenesis of rosacea. In this study, we investigated whether brimonidine gel could influence the number of mast cells (MCs) and mRnA levels of tryptase and chymase by evaluating the response of topical application of brimonidine gel to rosacea-like skin lesions in mice. | EXPERIMENTAL DESIGNThirty-five 7-week-old female Balb/c mice were used in this study (Dooyeol Biotech, Seoul, Korea). The experimental protocol was approved by the Animal Care Committee of Catholic University of Korea. The mice were divided into three groups: control (n=11), LL-37 (n=12), and LL-37 plus brimonidine (LL-37+ brimonidine; n=12). The mice in the LL-37 and LL-37+ brimonidine groups had LL-37 injected intradermally into shaved back skin to induce rosacea-like skin lesions.Immediately after the injection of LL-37 (40 μL), the mice in the LL-37+ brimonidine group had brimonidine tartrate 0.3...

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of mast cell infiltration in an LL‐37‐induced rosacea mouse model using topical brimonidine tartrate 0.33% gel

Kim

Jeong

et al. 2017

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…One important antimicrobial factor released by MCs is the cathlecidin LL-37 (20,21). Therefore, we examined the effect of LL-37 on E. faecalis.…”

Section: Fig 3 (A and B) Mcs Derived From Either Wild-type Tlr2mentioning

confidence: 99%

New Insights into the Antimicrobial Effect of Mast Cells against Enterococcus faecalis

et al. 2014

View full text Add to dashboard Cite

c Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. The pathogenesis of enterococcal infections has remained a relatively neglected field despite their obvious clinical relevance. The objective of this study was to characterize the interactions between mast cells (MCs), an innate immune cell population abundant in the intestinal lamina propria, and E. faecalis. This study was conducted with primary bone marrow-derived murine MCs. The results demonstrated that MCs exerted an antimicrobial effect against E. faecalis that was mediated both by degranulation, with the concomitant discharge of the antimicrobial effectors contained in the granules, and by the release of extracellular traps, in which E. faecalis was snared and killed. In particular, the cathelicidin LL-37 released by the MCs had potent antimicrobial effect against E. faecalis. We also investigated the specific receptors involved in the recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are critically involved in the MC recognition of E. faecalis, since MCs deficient in the expression of MyD88, an adaptor molecule required for signaling by most TLRs, were significantly impaired in their capacity to degranulate, to reduce E. faecalis growth as well as to release tumor necrosis factor alpha (TNF-␣) and interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was identified as the most prominent TLR involved in the recognition of E. faecalis by MCs. The results of this study indicate that MCs may be important contributors to the host innate immune defenses against E. faecalis.

show abstract

“…Mastcells are key mediators of cathelicidin-initiated skin inflammation in rosacea, 13 but anti-histaminerg treatment is rarely effective in its treatment.…”

Section: Pathophysiology Of Rosaceamentioning

confidence: 99%

Rosacea: a clinical review

Mikkelsen¹,

Holmgren²,

Kjellman³

et al. 2016

Dermatol Reports

View full text Add to dashboard Cite

Rosacea is a field within dermatology with new insight within immunological research and new treatment-algorithm. Patient education on rosacea and appropriate treatments is an important aspect in helping patients succeed with therapy. Treatment should be tailored to each individual patient, taking into account: symptoms, trigger factors, patients’ wishes, most bothersome symptoms, psychological aspect, individual needs. A combination of clinical therapies to treat different symptoms concomitantly may offer the best possible outcomes for the patient. In this review article we describe these aspects.

show abstract

Mast Cells Are Key Mediators of Cathelicidin-Initiated Skin Inflammation in Rosacea

Cited by 163 publications

References 28 publications

Inhibition of mast cell infiltration in an LL‐37‐induced rosacea mouse model using topical brimonidine tartrate 0.33% gel

Inhibition of mast cell infiltration in an LL‐37‐induced rosacea mouse model using topical brimonidine tartrate 0.33% gel

New Insights into the Antimicrobial Effect of Mast Cells against Enterococcus faecalis

Rosacea: a clinical review

Contact Info

Product

Resources

About