α‐MSH reduces the internalization of <i>Staphylococcus aureus</i> and down‐regulates HSP 70, integrins and cytokine expression in human keratinocyte cell lines

Donnarumma, Giovanna; Paoletti, Iole; Buommino, Elisabetta; Tufano, Maria Antonietta; Baroni, Adone

doi:10.1111/j.0906-6705.2004.00218.x

Cited by 21 publications

(15 citation statements)

References 42 publications

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“…Our results showed that PGA-α-MSH down-regulated IL-6, TGF-β, and TNF-α expression induced by Pg- LPS stimulation in EC and FB cultures. Similar results have been demonstrated in vitro studies with human bronchial epithelial cells, pre-stimulated with Pg -LPS [21] or on fibroblasts, pre-stimulated with E. Coli -LPS [11] and with keratinocytes activated by S. aureus [31]. These data showed the anti-inflammatory properties PGA-α-MSH in gingival cells and that this effect was time dependent and appeared more efficient in FB than in EC.…”

Section: Discussionsupporting

confidence: 82%

Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response

et al. 2015

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Alpha-melanocyte stimulating hormone (α-MSH) is involved in normal skin wound healing and also has anti-inflammatory properties. The association of α-MSH to polyelectrolyte layers with various supports has been shown to improve these anti-inflammatory properties. This study aimed to evaluate the effects of nanofibrous membrane functionalized with α-MSH linked to polyelectrolyte layers on gingival cell inflammatory response. Human oral epithelial cells (EC) and fibroblasts (FB) were cultured on plastic or electrospun Poly-ε-caprolactone (PCL) membranes with α-MSH covalently coupled to Poly-L-glutamic acid (PGA-α-MSH), for 6 to 24 h. Cells were incubated with or without Porphyromonas gingivalis lipopolysaccharide (Pg-LPS). Cell proliferation and migration were determined using AlamarBlue test and scratch assay. Expression of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor-beta (TGF-β) was evaluated using RT-qPCR method. Cell cultures on plastic showed that PGA-α-MSH reduced EC and FB migration and decreased IL-6 and TGF-β expression in Pg-LPS stimulated EC. PGA-α-MSH functionalized PCL membranes reduced proliferation of Pg-LPS stimulated EC and FB. A significant decrease of IL-6, TNF-α, and TGF-β expression was also observed in Pg-LPS stimulated EC and FB. This study showed that the functionalization of nanofibrous PCL membranes efficiently amplified the anti-inflammatory effect of PGA-α-MSH on gingival cells.

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Section: Discussionsupporting

confidence: 82%

Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response

et al. 2015

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“…The sequence of this neuropeptide is Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-TrpGly-Lys-Pro-Val-NH 2 . It controls inflammation and high temperature through immunomodulation, downregulates several proinflammatory cytokines, and stimulates production of antiinflammatory cytokines such as interleukin-10 (IL-10) (2,14,23). The widespread distribution of this peptide and its receptor in many barrier cells such as keratinocytes and in various immune cells suggests its potential role in host defense.…”

mentioning

confidence: 99%

C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

Singh

Mukhopadhyay

2011

Antimicrob Agents Chemother

105

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Alpha-melanocyte-stimulating hormone (␣-MSH) is an endogenous neuropeptide that is known for its anti-inflammatory and antipyretic activities.We recently demonstrated that ␣-MSH possesses staphylocidal activity and causes bacterial membrane damage. To understand the role of its amino acid sequences in the staphylocidal mechanism, in the present study we investigated the antimicrobial activities of different fragments of ␣-MSH, i.e., ␣-MSH(6-13), ␣-MSH(11-13), and ␣-MSH(1-5), and compared them with that of the entire peptide. Our results showed that peptides containing the C-terminal region of ␣-MSH, namely, ␣-MSH(6-13) and ␣-MSH(11-13), efficiently killed >90% of both methicillin-sensitive and -resistant Staphylococcus aureus cells in the micromolar range and ϳ50% of these cells in the nanomolar range; their efficiency was comparable to that of the entire ␣-MSH, whereas the peptide containing the N-terminal region, ␣-MSH(1-5), was found to be ineffective against S. aureus. The antimicrobial activity of ␣-MSH and its C-terminal fragments was not affected by the presence of NaCl or even divalent cations such as Ca 2؉ and Mg 2؉ . Similar to the case for the parent peptide, ␣-MSH(6-13) and ␣-MSH(11-13) also depolarized and permeabilized Staphylococcus cells (ϳ70 to 80% of the cells were depolarized and lysed after 2 h of peptide exposure at micromolar concentrations). Furthermore, scanning and transmission electron microscopy showed remarkable morphological and ultrastructural changes on S. aureus cell surface due to exposure to ␣-MSH-based peptides. Thus, our observations indicate that C-terminal fragments of ␣-MSH retain the antimicrobial activity of entire peptide and that their mechanism of action is similar to that of full-length peptide. These observations are important and are critical in the rational design of ␣-MSH-based therapeutics with optimal efficacy.

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“…In the case of α-MSH, the indirect antibacterial effects are connected with multiple general anti-inflammatory properties. For example, in human keratinocytes α-MSH down-regulates β-1 integrins and heat shock surface protein 70, both of which are essential molecules in the invasion of keratinocytes by S. aureus [103]. Furthermore α-MSH down-regulates pro-inflammatory cytokine expression in human keratinocytes suggesting it has a protective role in both infection and inflammation [103].…”

Section: Therapeutic Potential In the Light Of In Vivo Studiesmentioning

confidence: 99%

“…For example, in human keratinocytes α-MSH down-regulates β-1 integrins and heat shock surface protein 70, both of which are essential molecules in the invasion of keratinocytes by S. aureus [103]. Furthermore α-MSH down-regulates pro-inflammatory cytokine expression in human keratinocytes suggesting it has a protective role in both infection and inflammation [103]. It is therefore tempting to speculate that taken together these data suggest a relationship between resolution of infection in vivo and the presence of action of NPs.…”

Section: Therapeutic Potential In the Light Of In Vivo Studiesmentioning

confidence: 99%

Direct and Indirect Antimicrobial Activities of Neuropeptides and their Therapeutic Potential

Augustyniak¹,

Nowak

Lundy

2012

CPPS

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As global resistance to conventional antibiotics rises we need to develop new strategies to develop future novel therapeutics. In our quest to design novel anti-infectives and antimicrobials it is of interest to investigate host-pathogen interactions and learn from the complexity of host defense strategies that have evolved over millennia. A myriad of host defense molecules are now known to play a role in protection against human infection. However, the interaction between host and pathogen is recognized to be a multifaceted one, involving countless host proteins, including several families of peptides. The regulation of infection and inflammation by multiple peptide families may represent an evolutionary failsafe in terms of functional degeneracy and emphasizes the significance of host defense in survival. One such family is the neuropeptides (NPs), which are conventionally defined as peptide neurotransmitters but have recently been shown to be pleiotropic molecules that are integral components of the nervous and immune systems. In this review we address the antimicrobial and anti-infective effects of NPs both in vitro and in vivo and discuss their potential therapeutic usefulness in overcoming infectious diseases. With improved understanding of the efficacy of NPs, these molecules could become an important part of our arsenal of weapons in the treatment of infection and inflammation. It is envisaged that targeted therapy approaches that selectively exploit the anti-infective, antimicrobial and immunomodulatory properties of NPs could become useful adjuncts to our current therapeutic modalities.

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α‐MSH reduces the internalization of Staphylococcus aureus and down‐regulates HSP 70, integrins and cytokine expression in human keratinocyte cell lines

Cited by 21 publications

References 42 publications

Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response

Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response

C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus

Direct and Indirect Antimicrobial Activities of Neuropeptides and their Therapeutic Potential

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