Interleukin-6 Treatment Augments Cutaneous Wound Healing in Immunosuppressed Mice

Gallucci, Randle M.; Sugawara, Takafumi; Yücesoy, Berran; Berryann, Kristi; Simeonova, Petia P.; Matheson, Joanna; Luster, Michael I.

doi:10.1089/10799900152547867

Cited by 81 publications

(63 citation statements)

References 45 publications

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“…However, its role in wound healing appears to be opposite to those of TNF-α or IL-1β. For example, treatment with IL-6 augmented wound healing in immunosuppressed mice (26). In line with this, Lin et al (27) reported delayed wound healing in IL-6-deficient mice.…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 82%

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

El-Hamoly

Hegedűs

Lakatos

et al. 2014

Mol Med

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Poly(ADP-ribosyl)ation (PARylation) is a protein modification reaction regulating various diverse cellular functions ranging from metabolism, DNA repair and transcription to cell death. We set out to investigate the role of PARylation in wound healing, a highly complex process involving various cellular and humoral factors. We found that topically applied poly[ADP-ribose] polymerase (PARP) inhibitors 3-aminobenzamide and PJ-34 accelerated wound closure in a mouse model of excision wounding. Moreover, wounds also closed faster in PARP-1 knockout mice as compared with wild-type littermates. Immunofluorescent staining for poly(ADP-ribose) (PAR) indicated increased PAR synthesis in scattered cells of the wound bed. Expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase and matrix metalloproteinase-9 was lower in the wounds of PARP-1 knockout mice as compared with control, and expression of IL-1β, cyclooxygenase-2, TIMP-1 and -2 also were affected. The level of nitrotyrosine (a marker of nitrating stress) was lower in the wounds of PARP-1 knockout animals as compared with controls. In vitro scratch assays revealed significantly faster migration of keratinocytes treated with 3-aminobenzamide or PJ34 as compared with control cells. These data suggest that PARylation by PARP-1 slows down the wound healing process by increasing the production of inflammatory mediators and nitrating stress and by slowing the migration of keratinocytes.

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Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 82%

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

El-Hamoly

Hegedűs

Lakatos

et al. 2014

Mol Med

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“…Increased cellular infiltration is followed by severe retinal damage. Interleukin (IL)-6 is a pleiotropic cytokine with a wide spectrum of biological activities in a broad variety of ocular inflammatory diseases and wound healing processes (10)(11)(12). IL-6 is an important mediator in a variety of diseases, including inflammatory, autoimmune and malignant diseases.…”

Section: Ycg063 Inhibits Pseudomonas Aeruginosa Lps-induced Inflammatmentioning

confidence: 99%

YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

Paeng

Park

Jung

et al. 2015

International Journal of Molecular Medicine

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Abstract. YCG063 is known as an inhibitor of reactive oxygen species (ROS); however, its intracellular mechanisms of action remain poorly understood. In the present study, we investigated the effects of YCG063 on the inflammatory response of Pseudomonas aeruginosa lipopolysaccharide (PA-LPS)-stimulated human retinal pigment epithelial cells (RPE cells). Human adult RPE cells (ARPE-19) were stimulated with PA-LPS. We then investigated the LPS-induced expression of several inflammatory mediators, such as interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and intracellular adhesion molecule-1 (ICAM-1) in the ARPE-19 cells. We performed an enzyme-linked immunosorbent assay (ELISA), western blot analysis, electrophoretic mobility shift assay (EMSA) and fluorescence-activated cell sorting (FACS) to elucidate the mechanisms involved in the anti-inflammatory effects of YCG063 in the PA-LPS-stimulated cells. The results revealed that treatment with YCG063 significantly inhibited the levels of IL-6, IL-8, MCP-1 and ICAM-1 in the PA-LPS-stimulated ARPE-19 cells. YCG063 also markedly inhibited the phosphorylation of AKT in the PA-LPS-stimulated cells. In addition, the activation of nuclear factor-κB (NF-κB) was also attenuated folllowing treatment with YCG063. ROS were not generated in the PA-LPS-stimulated cells. In conclusion, our data indicate that YCG063 may prove to be a potential protective agent against inflammation, possibly through the downregulation of Toll-like receptor 2 (TLR2) and the AKT-dependent NF-κB activation pathway in PA-LPSstimulated ARPE-19 cells. Furthermore, this anti-inflammatory activity occurred through ROS-independent signaling pathways. IntroductionEndophthalmitis is an uncommon intraocular inflammatory condition, but it may result in partial or complete vision loss. It may occur as a complication of intraocular surgery or as a result of non-surgical trauma or systemic infection (1). Bacterial endophthalmitis is an infection of the intraocular cavities that usually occurs following the introduction of microbial organisms into the eye (2). During a bacterial infection, irreversible damage to the photoreceptor cells of the retina frequently occurs (3). Among the bacterial pathogens, Pseudomonas aeruginosa (PA), a Gram-negative rod rod-shaped organism, is frequently a cause of nosocomial infections (4). PA can cause ocular infections, such as keratitis and endophthalmitis (5). YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

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“…Previously it was found that cutaneous wound healing in IL-6 gene-deficient mice was significantly slower than that in wild type control mice [134][135][136]. It was found that gene expression enhancement of IL-1, chemokines, adhesion molecules, TGF-β1 and VEGF at the wound sites was significantly reduced in IL-6-deficient mice [136].…”

Section: Safety Profile Of Tocilizumabmentioning

confidence: 99%

Targeting of Interleukin-6 for the Treatment of Rheumatoid Arthritis: A Review and Update

Ogata¹

2014

Rheumatology (Sunnyvale)

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Tanaka et al., Rheumatol Curr Res 2013, S4 http://dx.doi.org/10.4172/2161-1149 Review ArticleOpen Access AbstractRheumatoid Arthritis (RA) is a chronic inflammatory disease, characterized by persistent joint inflammation, systemic inflammation and immunological abnormalities. Since IL-6 plays a major role in the development of these characteristics, its targeting could reasonably be expected to constitute a novel therapeutic strategy for the treatment of RA. Tocilizumab, a humanized anti-human IL-6 receptor monoclonal antibody, has demonstrated its outstanding clinical efficacy and tolerable safety profile in phase III clinical trials for RA patients, resulting in its worldwide approval for moderate-to-severe active RA. Post-marketing clinical trials have confirmed its efficacy. This success led to the development of various other IL-6 inhibitors. Further clinical studies including head-to-head comparative studies, and clarification of the mechanisms through which tocilizumab exerts its clinical effects can be expected to identify RA patients who should be treated with tocilizumab as a first-line biologic. In addition, recent case reports and pilot studies indicate that therapies targeting IL-6 will be widely applicable to the treatment of various intractable immune-mediated diseases.

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Interleukin-6 Treatment Augments Cutaneous Wound Healing in Immunosuppressed Mice

Cited by 81 publications

References 45 publications

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

Activation of Poly(ADP-Ribose) Polymerase-1 Delays Wound Healing by Regulating Keratinocyte Migration and Production of Inflammatory Mediators

YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

Targeting of Interleukin-6 for the Treatment of Rheumatoid Arthritis: A Review and Update

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