Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay

Krzystek−Korpacka, Małgorzata; Kędzior, Krzysztof; Masłowski, Leszek; Mierzchała, Magdalena; Bednarz−Misa, Iwona; Bronowicka-Szydełko, Agnieszka; Kubiak, Joanna; Gacka, Małgorzata; Płaczkowska, Sylwia; Gamian, Andrzej

doi:10.17219/acem/103845

Cited by 12 publications

(7 citation statements)

References 33 publications

(51 reference statements)

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“…The previous study reported that IL-1, IL-6, and IL-8 significantly upregulated in wound fluids from patients with chronic wounds [50]. Furthermore, non-healing wounds of patients with comorbidity (diabetes and/or cardiovascular disease) found the increasing in cytokines (IL-1β, IL-4, IL-6, IL-8, TNF-α) and growth factors (FGF2, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), VEGF-A, and PDGF-BB) levels [51]. So, excessive secretion of cytokines would interfere normal healing process.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

High Efficiency In Vitro Wound Healing of Dictyophora indusiata Extracts via Anti-Inflammatory and Collagen Stimulating (MMP-2 Inhibition) Mechanisms

Nazir

Linsaenkart

Khantham

et al. 2021

JoF

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Dictyophora indusiata or Phallus indusiatus is widely used as not only traditional medicine, functional foods, but also, skin care agents. Biological activities of the fruiting body from D. indusiata were widely reported, while the studies on the application of immature bamboo mushroom extracts were limited especially in the wound healing effect. Wound healing process composed of 4 stages including hemostasis, inflammation, proliferation, and remodelling. This study divided the egg stage of bamboo mushroom into 3 parts: peel and green mixture (PGW), core (CW), and whole mushroom (WW). Then, aqueous extracts were investigated for their nucleotide sequencing, biological compound contents, and wound healing effect. The anti-inflammatory determination via the levels of cytokine releasing from macrophages, and the collagen stimulation activity on fibroblasts by matrix metalloproteinase-2 (MMP-2) inhibitory activity were determined to serve for the wound healing process promotion in the stage 2–4 (wound inflammation, proliferation, and remodelling of the skin). All D. indusiata extracts showed good antioxidant potential, significantly anti-inflammatory activity in the decreasing of the nitric oxide (NO), interleukin-1 (IL-1), interleukin-1 (IL-6), and tumour necrosis factor-α (TNF-α) secretion from macrophage cells (p < 0.05), and the effective collagen stimulation via MMP-2 inhibition. In particular, CW extract containing high content of catechin (68.761 ± 0.010 mg/g extract) which could significantly suppress NO secretion (0.06 ± 0.02 µmol/L) better than the standard anti-inflammatory drug diclofenac (0.12 ± 0.02 µmol/L) and their MMP-2 inhibition (41.33 ± 9.44%) was comparable to L-ascorbic acid (50.65 ± 2.53%). These findings support that CW of D. indusiata could be an essential natural active ingredient for skin wound healing pharmaceutical products.

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Section: Anti-inflammatory Activitymentioning

confidence: 99%

High Efficiency In Vitro Wound Healing of Dictyophora indusiata Extracts via Anti-Inflammatory and Collagen Stimulating (MMP-2 Inhibition) Mechanisms

Nazir

Linsaenkart

Khantham

et al. 2021

JoF

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“…However, limited animal studies have linked PRMT overexpression with obesity, nonalcoholic fatty liver disease, and diabetic retinopathy [37, 38] and DDAH downregulation with diabetic retinopathy [38] and impaired vascular homeostasis [39]. PRMT and DDAH might be altered more strongly among patients with chronic wounds than without as they are positively (PRMTs) and negatively (DDAHs) affected by inflammatory mediators [31, 40] and, as we have previously demonstrated, chronic wounds are accompanied by systemic elevation in proinflammatory cytokines [41].…”

Section: Discussionmentioning

confidence: 98%

“…Among others, they induce the expression of iNOS [16] but inhibit that of eNOS [52, 53] and contribute to ADMA accumulation [31, 40]. Recently, we have demonstrated that chronic wounds are accompanied by systemic elevation of IL-1 β , IL-4, IL-6, IL-8, FGF-2, MIP-1 α , PDGF-BB, and VEGF-A [41]. Also, markedly elevated CRP and reduced HDL in patients with chronic wounds compared to those with similar cardiometabolic burden are indicative of a higher grade of inflammation in the former.…”

Section: Discussionmentioning

confidence: 99%

“…G-CSF and GM-CSF are hematopoietic cytokines displaying immunomodulatory and antibiotic-enhancing activities with a proven beneficial effect on wound healing [54–56]. Their concentrations are reduced in patients with chronic wounds [41]. Park et al [57] demonstrated that G-CSF exerts a protective effect on endothelial cells via stimulating eNOS expression and phosphorylation and thus enhancing NO synthesis and signalling.…”

Section: Discussionmentioning

confidence: 99%

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Metabolites of the Nitric Oxide (NO) Pathway Are Altered and Indicative of Reduced NO and Arginine Bioavailability in Patients with Cardiometabolic Diseases Complicated with Chronic Wounds of Lower Extremities: Targeted Metabolomics Approach (LC-MS/MS)

Krzystek−Korpacka

Wiśniewski

Fleszar

et al. 2019

Oxidative Medicine and Cellular Longevity

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Objective. The status of metabolites of the nitric oxide (NO) pathway in patients with chronic wounds in the course of cardiometabolic diseases is largely unknown. Yet arginine supplementation and citrulline supplementation as novel therapeutic modalities aimed at increasing NO are tested. Material and Methods. Targeted metabolomics approach (LC-MS/MS) was applied to determine the concentrations of L-arginine, L-citrulline, asymmetric and symmetric dimethylarginines (ADMA and SDMA), and arginine/ADMA and arginine/SDMA ratios as surrogate markers of NO and arginine availability in ulnar and femoral veins, representing systemic and local levels of metabolites, in patients with chronic wounds in the course of cardiometabolic diseases (n=59) as compared to patients without chronic wounds but with similar cardiometabolic burden (n=55) and healthy individuals (n=88). Results. Patients with chronic wounds had significantly lower systemic L-citrulline and higher ADMA and SDMA concentrations and lower L-arginine/ADMA and L-arginine/SDMA as compared to healthy controls. The presence of chronic wounds in patients with cardiometabolic diseases was associated with decreased L-arginine but with increased L-citrulline, ADMA, and SDMA concentrations and decreased L-arginine/ADMA and L-arginine/SDMA. Serum obtained from the ulnar and femoral veins of patients with chronic wounds differed by L-arginine concentrations and L-arginine/SDMA ratio, both lower in the femoral vein. Wound etiology affected L-citrulline and SDMA concentrations, lower and higher, respectively, in patients with venous stasis, and the L-arginine/SDMA ratio—lower in venous stasis. The wound type affected L-arginine/ADMA and citrulline—lower in patients with ulcerations or gangrene. IL-6 was an independent predictor of L-arginine/ADMA, VEGF-A of ADMA, G-CSF of L-arginine/SDMA, and GM-CSF of L-citrulline and SDMA. Conclusion. Chronic wounds in the course of cardiometabolic diseases are associated with reduced NO and arginine availability due to ADMA and SDMA accumulation rather than arginine deficiency, not supporting its supplementation. Wound character seems to affect NO bioavailability and wound etiology—arginine bioavailability. Arginine concentration and its availability are more markedly reduced at the local level than the systemic level.

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“…In animals with CKD, signs of epidermal cell dystrophy, edema, and hemorrhages in the granulation tissue performing the wound defect were observed at all periods of the experiment . Circulatory disorders and inflammatory infiltration, retardation of reepithelialization and the formation of an extracellular matrix, accumulation of cellular decay products and proteases in the tissue fluid are characteristic of chronic wounds, including those occurring against the background of systemic diseases (Bodnár et al, 2018;Krzystek-Korpacka et al, 2019). The duration of the healing of such wounds is due to the predominance of the phase of inflammation in the regeneration process.…”

Section: Discussionmentioning

confidence: 99%

Features of skin wound healing in rats with experimental chronic kidney disease

Pavlov

Litvinova

Babenko

2021

Regul. Mech. Biosyst.

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Chronic kidney disease negatively affects the morphofunctional state of all organs due to hemodynamic and metabolic disorders. Changes in the content of cytokines observed in kidney diseases, which regulate the processes of inflammation and tissue repair, can complicate the course of the wound process. This research aimed to study disorders in the process of skin wound repair due to changes in the dynamics of production of interleukins IL-1β, IL-6, IL-10, IL-4, growth factors bFGF and VEGF in animals with experimental chronic kidney disease. The levels of interleukins and growth factors were determined on the 7th, 14th and 28th days after surgical modeling of wounds in the blood of rats with experimental chronic kidney disease and animals of the control group. To assess the dynamics and quality of wound healing, a semi-quantitative histological analysis was performed. The study showed an increase in the content of pro-inflammatory interleukins in the group of sick rats: on the 7th day the level of IL-1β was 1.19 times higher, and IL-6 – 1.55 times, on the 14th day the level of IL-1β was 1.37 times in comparison with the control group. The maximum increase in the concentration of anti-inflammatory interleukins was noted on the 28th day: IL-4 was 2.10 times higher, IL-10 – 1.39 times higher than in the control group. The content of bFGF and VEGF in animals of the control group reached its maximum on the 7th day, and in animals with chronic kidney disease – on the 15th day after surgery. Semi-quantitative histological analysis showed a decrease in indicators in the group of sick animals: the number of fibroblasts and collagen deposition – on the 7th day, reepithelialization – on the 28th day. A persistent increase in the number of polymorphonuclear leukocytes was also noted at all periods of the experiment: by 1.38, 1.99, and 9.82 times – on the 7th, 14th, and 28th days, respectively. The study showed that the dynamics of the production of interleukins and growth factors were impaired in rats with chronic kidney disease. In the process of damage regeneration in sick animals, pro-inflammatory mechanisms prevailed with the involvement of a large number of immunocompetent cells, as a result, skin wounds took longer to heal.

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Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay

Abstract: Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay.

Cited by 12 publications

References 33 publications

High Efficiency In Vitro Wound Healing of Dictyophora indusiata Extracts via Anti-Inflammatory and Collagen Stimulating (MMP-2 Inhibition) Mechanisms

High Efficiency In Vitro Wound Healing of Dictyophora indusiata Extracts via Anti-Inflammatory and Collagen Stimulating (MMP-2 Inhibition) Mechanisms

Metabolites of the Nitric Oxide (NO) Pathway Are Altered and Indicative of Reduced NO and Arginine Bioavailability in Patients with Cardiometabolic Diseases Complicated with Chronic Wounds of Lower Extremities: Targeted Metabolomics Approach (LC-MS/MS)

Features of skin wound healing in rats with experimental chronic kidney disease

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