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Cellular sources and inducers of cytokines present in acute wound fluid

Published on May 1, 2011in Wound Repair and Regeneration 2.95
· DOI :10.1111/j.1524-475X.2011.00668.x
Øystein Grimstad5
Estimated H-index: 5
(Norwegian University of Science and Technology),
Øystein Sandanger9
Estimated H-index: 9
(Norwegian University of Science and Technology)
+ 4 AuthorsTerje Espevik72
Estimated H-index: 72
(Norwegian University of Science and Technology)
Abstract
Acute wounds contain many biological active molecules, including several cytokines and growth factors. However, the cellular sources of each molecule, as well as the stimuli inducing them, are poorly characterized. We quantified the levels of 27 cytokines, chemokines, and growth factors in acute wound fluid in a luminex-based assay. The acute wound fluid contained particularly high levels of IL-6 and IL-8, as well as elevated levels of MCP-1, IL-1RA, PDGF, IP-10, IFN-γ, and TNF-α. Surprisingly, the amounts of IL-1β and IL-10 were relatively low. To characterize the cellular sources of these molecules, we analyzed supernatants from monocytes, neutrophils, keratinocytes, fibroblasts, and endothelial cells stimulated with pro- and anti inflammatory cytokines, and different Toll-like receptor (TLR) ligands. The different cell types showed overlapping but distinct patterns of production of signal molecules, as well as sensitivity to ligands. Among pro-inflammatory cytokines, IL-1β was the most potent inducer of signal molecule production. Furthermore, keratinocytes and endothelial cells were in particular responsive to the Toll-like receptor-3 ligand poly I:C. New interactions between cytokines and growth factors were revealed, which may have important roles in wound healing, including IL-1β-induced IFN-γ and IL-10-induced VEGF.
  • References (33)
  • Citations (41)
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References33
Newest
Masaaki Murakami45
Estimated H-index: 45
,
Yasunobu Arima13
Estimated H-index: 13
,
Toshio Hirano110
Estimated H-index: 110
3 Citations
Published on Feb 1, 2010in British Journal of Dermatology 6.13
Julius Renne10
Estimated H-index: 10
(Hannover Medical School),
V. Schäfer1
Estimated H-index: 1
(Hannover Medical School)
+ 1 AuthorsMiriam Wittmann25
Estimated H-index: 25
(Hannover Medical School)
Summary Background Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases. Objectives In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes. Methods We used a human coculture model with keratinocytes grown...
51 Citations Source Cite
Published on Dec 1, 2009in Nature Medicine 32.62
Yuping Lai23
Estimated H-index: 23
(University of California, San Diego),
Anna Di Nardo18
Estimated H-index: 18
(University of California, San Diego)
+ 11 AuthorsSonja von Aulock32
Estimated H-index: 32
(University of Konstanz)
The normal microflora of the skin includes staphylococcal species that will induce inflammation when present below the dermis but are tolerated on the epidermal surface without initiating inflammation. Here we reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. This inhibition is mediated by staphylococcal lipoteichoic acid (LTA) and acts selectively on keratinocytes triggered through Toll-like receptor 3(TLR3). We show that TLR3 activation is re...
350 Citations Source Cite
Published on Jul 1, 2009in Seminars in Cell & Developmental Biology 6.14
Sabine A. Eming36
Estimated H-index: 36
(University of Cologne),
Matthias Hammerschmidt72
Estimated H-index: 72
(University of Cologne)
+ 1 AuthorsAxel Roers40
Estimated H-index: 40
Abstract Although tremendous progress has been achieved in understanding the molecular basis of tissue repair and regeneration in diverse model organisms, the tendency of mammals for imperfect healing and scarring rather than regeneration remains unexplained. Moreover, conditions of impaired wound healing, e.g. non-healing skin ulcers associated with diabetes mellitus or vascular disease, as well as excessive scarring, represent major clinical and socio-economical problems. The development of in...
156 Citations Source Cite
Published on Jun 1, 2008in Angiogenesis 4.35
Janice A. Nagy54
Estimated H-index: 54
(Beth Israel Deaconess Medical Center),
Laura E. Benjamin32
Estimated H-index: 32
(Beth Israel Deaconess Medical Center)
+ 2 AuthorsHarold F. Dvorak110
Estimated H-index: 110
(Beth Israel Deaconess Medical Center)
The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both pro...
342 Citations Source Cite
Published on Mar 1, 2008in International Journal of Legal Medicine 2.32
Masataka Takamiya17
Estimated H-index: 17
(Iwate Medical University),
Sachiko Fujita7
Estimated H-index: 7
(Iwate Medical University)
+ 1 AuthorsYasuhiro Aoki21
Estimated H-index: 21
(Iwate Medical University)
We performed quantification of IL 2, IL 4, IL 6, IL 8, IL 10, GM-CSF, IFN γ, and TNF α in human dermal wounds for wound age estimation. The proliferation of dermal cells and infiltration of inflammatory cells were also analyzed. Neutrophils and macrophages were detected from 2 h post-injury, and strong infiltrations were seen at 33–49 h. T and B lymphocytes also infiltrated simultaneously from 71 h. Strong proliferation of fibroblasts were shown from 246 h, and thickening of the epidermis from 7...
45 Citations Source Cite
Published on Feb 1, 2007in Journal of Investigative Dermatology 6.45
M C Lebre10
Estimated H-index: 10
(University of Amsterdam),
Aar van der A. M. G8
Estimated H-index: 8
(University of Amsterdam)
+ 4 AuthorsEsther C. de Jong37
Estimated H-index: 37
(University of Amsterdam)
Keratinocytes are continuously in contact with external stimuli and have the capacity to produce several soluble mediators. Pathogen-associated molecular patterns (PAMPs) are recognized, among others, by Toll-like receptors (TLRs). The functional responses of keratinocytes to different PAMPs have not yet been fully established. Here we show that keratinocytes constitutively express TLR1, 2, 3, 4, 5, 6, 9, and 10 mRNA, but not TLR7 and 8. Stimulation of keratinocytes with TLR3, 4, 5, and 9 ligand...
300 Citations Source Cite
Published on Jan 1, 2007in Clinics in Dermatology 2.06
Jie Li6
Estimated H-index: 6
(University of Miami),
Juan Chen1
Estimated H-index: 1
(University of Miami),
Robert S. Kirsner55
Estimated H-index: 55
(University of Miami)
Wound healing is a complex process that can be divided into at least 3 continuous and overlapping processes: an inflammatory reaction, a proliferative process leading to tissue restoration, and, eventually, tissue remodeling. Wound healing processes are strictly regulated by multiple growth factors and cytokines released at the wound site. Although the desirable final result of coordinated healing would be the formation of tissue with a similar structure and comparable functions as with intact s...
518 Citations Source Cite
Published on Jun 28, 2006in Wound Repair and Regeneration 2.95
Gaetano Di Vita14
Estimated H-index: 14
,
Rosalia Patti15
Estimated H-index: 15
+ 7 AuthorsEnrico Cillari24
Estimated H-index: 24
Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1α, IL-1 ra, interferon-y, vascular endothelial growth ...
30 Citations Source Cite
Mikiko Tohyama26
Estimated H-index: 26
(Ehime University),
Xiuju Dai17
Estimated H-index: 17
(Ehime University)
+ 9 AuthorsHiroshi Nagai5
Estimated H-index: 5
(Ehime University)
Abstract MIP-1α, a CC chemokine, recruits monocytes, natural killer cells, lymphocytes, and neutrophils, and plays a critical role in viral infection. Since, the lesional epidermis of herpes zoster expressed MIP-1α, we hypothesized that keratinocytes produce MIP-1α in response to virus-associated dsRNA via TLR3. To investigate this, we examined cultured human keratinocytes for MIP-1α production induced by poly(I:C), a TLR3 ligand. Poly(I:C) treatment induced MIP-1α production, interestingly, pol...
31 Citations Source Cite
Cited By41
Newest
Published on Feb 1, 2019in Molecular and Cellular Biochemistry 2.56
Takumi Yamane7
Estimated H-index: 7
(Tokyo University of Agriculture),
Mari Shimura2
Estimated H-index: 2
(Tokyo University of Agriculture)
+ 2 AuthorsYuichi Oishi13
Estimated H-index: 13
(Tokyo University of Agriculture)
Adequate nutrition is required to maintain healthy skin integrity, and malnourished patients with poor protein diet often experience delayed wound healing. Understanding the cellular mechanisms of protein malnutrition will justify the importance of optimal protein diets in health and disease defense. Therefore in the present study, we examined the effects of changes in wound fluid composition and its function caused by protein malnutrition on wound healing. Rats were fed a control (CO; 20% prote...
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Published on Feb 1, 2018in Cytokine 3.51
Zhang Ying Zhu (Shantou University), Cong Zhuo Jia (Shantou University)+ 1 AuthorsLi Wang (Shantou University)
Abstract Polyriboinosinic-polyribocytidylic acid (polyI:C) is a viral dsRNA analoguethat promotes wounds healing, accelerates re-epithelialization, granulation and neovascularization, and induces pro-inflammatory cytokine release. Little is known about polyI:C mediated induction of inflammatory mediators in human dermal fibroblast (HDFs), which form the primary scaffold for epithelial cells covering the wound. Here, we found that polyI:C enhances IL-6 and IL-8 mRNA expression and induces of IL-6...
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Published on Dec 1, 2017in BMC Immunology 2.62
Kazuhide Takada1
Estimated H-index: 1
(Nihon University),
Shihoko Komine-Aizawa6
Estimated H-index: 6
(Nihon University)
+ 4 AuthorsSatoshi Hayakawa24
Estimated H-index: 24
(Nihon University)
Delayed wound healing reduces the quality of life (QOL) of patients. Thus, understanding the mechanism of wound healing is indispensable for better management. However, the role of innate immunity in wound healing is thus far unknown. Recently the involvement of TLR3 in wound healing has been evaluated. The systemic administration of polyriboinosinic-polyribocytidylic acid (poly I:C ; a substitute for viral dsRNA and a ligand of toll-like receptor 3), enhances wound healing in vivo. The aim of t...
6 Citations Source Cite
Published on Nov 1, 2017in Journal of Biomaterials Applications 2.08
Krystal R. Fontenot6
Estimated H-index: 6
,
J. Vincent Edwards11
Estimated H-index: 11
+ 5 AuthorsDorne R. Yager24
Estimated H-index: 24
Interfacing nanocellulosic-based biosensors with chronic wound dressings for protease point of care diagnostics combines functional material properties of high specific surface area, appropriate surface charge, and hydrophilicity with biocompatibility to the wound environment. Combining a protease sensor with a dressing is consistent with the concept of an intelligent dressing, which has been a goal of wound-dressing design for more than a quarter century. We present here biosensors with a nanoc...
3 Citations Source Cite
Published on Sep 1, 2017in Clinical Immunology 3.56
Francielle Rodrigues Guimarães1
Estimated H-index: 1
(University of São Paulo),
Helioswilton Sales-Campos6
Estimated H-index: 6
(University of São Paulo)
+ 8 AuthorsLúcia Helena Faccioli36
Estimated H-index: 36
(University of São Paulo)
Abstract To analyze the participation of the enzyme 5-lipoxygenase (5-LO) in skin repair, WT wounds were compared to those in 5-LO deficient mice (5-LO −/− ), which presented faster closure and reduced inflammatory infiltrate in the skin, together with increased CD4 regulatory T cells markers in the draining lymph nodes. The 5-LO −/− wounds also had diminished TNF-α, CCL11, CCL7, CCL2, CXCL9, CCR1 and CXCR2 mRNA expression in the lesions, besides differential extracellular matrix remodeling. Fur...
2 Citations Source Cite
Published on Jul 1, 2017in Journal of Applied Biomedicine 1.78
Jana Juráňová2
Estimated H-index: 2
(Palacký University, Olomouc),
Jana Franková5
Estimated H-index: 5
(Palacký University, Olomouc),
Jitka Ulrichová40
Estimated H-index: 40
(Palacký University, Olomouc)
Abstract The epidermis is the external layer of the skin and is composed mainly of keratinocytes. Therefore, keratinocytes play an indispensable role as inherent constituents of the skin barrier in physical defenses against environmental threats. Keratinocytes also exert an active protective role against invasion by pathogens. This competency is of particular importance when physical defenses fail as a consequence of skin injury. During the inflammatory phase of healing, keratinocytes act as imm...
5 Citations Source Cite
Published on Oct 26, 2016in Sensors 2.48
J. Vincent Edwards11
Estimated H-index: 11
,
Krystal R. Fontenot6
Estimated H-index: 6
+ 3 AuthorsBrian Condon21
Estimated H-index: 21
Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride...
9 Citations Source Cite
Published on Oct 1, 2016in Current Opinion in Cell Biology 10.02
Tanya J. Shaw16
Estimated H-index: 16
(King's College London),
Paul Martin48
Estimated H-index: 48
A skin wound requires several cell lineages to exhibit considerable plasticity as they migrate towards and over the site of damage to contribute to repair. The keratinocytes that re-epithelialize the tissue, the dermal fibroblasts and potentially other mesenchymal stem cell populations that repopulate damaged connective tissue, the immune cells that counter infections, and endothelial cells that re-establish blood supply and facilitate the immune response – all of these cells are ‘dynamic’ in th...
48 Citations Source Cite
Published on Oct 1, 2016in Carbohydrate Polymers 5.16
Henriette R. Nordli4
Estimated H-index: 4
(Norwegian University of Science and Technology),
Gary Chinga-Carrasco21
Estimated H-index: 21
+ 1 AuthorsBrita Pukstad8
Estimated H-index: 8
(Norwegian University of Science and Technology)
Abstract Wood cellulose nanofibrils (CNF) have been suggested as a potential wound healing material, but its utilization is limited by FDA requirements regarding endotoxin levels. In this study a method using sodium hydroxide followed by TEMPO mediated oxidation was developed to produce ultrapure cellulose nanofibrils, with an endotoxin level of 45 endotoxin units/g (EU/g) cellulose. Scanning transmission electron microscopy (S(T)EM) revealed a highly nanofibrillated structure (lateral width of ...
20 Citations Source Cite
Published on Mar 1, 2016in Wound Repair and Regeneration 2.95
Ju Hyeong Park3
Estimated H-index: 3
(Kyung Hee University),
Suna Kim4
Estimated H-index: 4
(Kyung Hee University)
+ 1 AuthorsYoungsook Son19
Estimated H-index: 19
(Kyung Hee University)
Diabetic ulceration is one of the most debilitating complications of diabetes and is the main cause of amputation. The diabetic environment is characterized by prolonged inflammation and abnormal angiogenesis, leading to delayed wound healing. Thus, regulation of inflammation and neovascularization is considered a desirable target for diabetes. The critical purpose of this study was to determine whether systemically administered Substance P (SP) could promote wound healing in diabetic environmen...
17 Citations Source Cite