The role of cytokines, chemokines and growth factors in extraction socket healing

2021 ◽  
Vol 26 (1) ◽  
pp. 58-63
Author(s):  
N. L. Erokina ◽  
A. V. Lepilin ◽  
A. Yu. Mironov ◽  
N. B. Zakharova ◽  
S. B. Fishtchev

Relevance. Reparative processes in the extraction socket include hemostasis, inflammation, proliferation and tissue remodelling. These processes are caused by mediators which determine interactions in the immunoregulatory, cytokine network. After the tooth extraction, pro- and anti-inflammatory mediators are unbalanced. The number of macrophages, lymphocytes, neutrophils releasing lysosomal enzymes increases in the surrounding tissues, and it leads to cleaning of the extraction socket from the damaged tissues and microorganisms. The growth factors are of great importance for reparative processes. The level of cytokines, chemokines and growth factors in biological fluids is the assessment criterium of various physiological and pathological processes and effectiveness of the treatment procedures. Purpose – to assess the activity of the wound healing processes by studying the level of cytokines/ chemokines and growth factors in the extraction socket. Materials and methods. The data received on examination of 40 patients was used in the study. 20 of the patients had their teeth extracted for chronic periodontitis and the socket healing was studied by clinical and laboratory findings (seven mediators of immunoregulatory processes were studied). The comparison group consisted of 20 subjects without periodontal pathology. Results. Clinical data, typical for the normal socket healing, are characterized by the certain content of immunoregulatory mediators (IL1β and IL6 – proinflammatory cytokines, IL8 and MCP1 – chemokines, RAIL1 – anti-inflammatory cytokine, VEGF and TGFβ1- growth factors). The content of proinflammatory cytokines and chemokines was detected to increase in the socket on the first day after the extraction, which indicates the activity of the local inflammatory process. The level of RAIL 1 and VEGF and TGFβ1 growth factors increases in the extraction socket five days later. Conclusion. The post-surgical activity of the inflammatory and regenerative processes in the tissues is revealed by the level of cytokines/ chemokines on the first day after surgery and the level of growth factors and RAIL1 in the socket discharge on the fifth day after surgery.

2021 ◽  
Vol 10 (21) ◽  
pp. 4801
Author(s):  
José A. Fernández-Albarral ◽  
Miguel A. Martínez-López ◽  
Eva M. Marco ◽  
Rosa de Hoz ◽  
Beatriz Martín-Sánchez ◽  
...  

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.


2021 ◽  
Vol 17 (7) ◽  
pp. 534-551
Author(s):  
K.P. Zak ◽  
V.V. Popova ◽  
V.L. Orlenko ◽  
O.V. Furmanova ◽  
N.D. Tronko

The paper analyzes the current literature data and the results of our own researches concerning the state of the cytokine network: pro- and anti-inflammatory cytokines (interleukin (IL) 1α, IL-1β, IL-4, IL-6, IL-10, IL-17 and tumor necrosis factor (TNF) α), α- and β-chemokines, including IL-8 and IL-16, as well as adipokines (leptin and adiponectin) in the peripheral blood of patients with type 2 diabetes (T2D) with normal and increased body weight/obesity. It has been shown that patients with T2D are cha­racterized by an increased content of proinflammatory cytokines (IL-1, IL-6, IL-17, TNFα), α- and β-chemokines in the peripheral blood, including IL-8 and IL-16, as well as leptin with a decrease in adiponectin content. In lean patients (with body mass index (BMI) < 25.5 kg/m2) compared to lean normoglycemic individuals from the control group (BMI < 25.5 kg/m2), there is a small but significant increase in IL-1β, IL-6, IL-17, TNFα and leptin, which, as BMI increases, significantly increases in severe obesity (BMI > 30.0 kg/m2), especially in obese women (BMI > 35.0 kg/m2). Similarly, an increase in proinflammatory cytokines is observed in normoglycemic people, but not as signifi­cant as in T2D. Less clear data were obtained when during determination of the anti-inflammatory cytokines IL-4 and IL-10, which is explained by a significant polymorphism of their genes, and both protective and compensatory effects on pro-inflammatory cytokine rise. In T2D patients, especially those with obesity, there is an increase in the leptin level and a decrease in the adiponectin content. The severity of the course and the percentage of mortality are closely associated with the BMI of patients. The effectiveness of the fight against an increase in the incidence of T2D should be primarily aimed at preventing obesity, and in case of already developed T2D — at reducing concomitant obesity. The analysis of the data presented also suggests that a sharp increase in the content of pro-inflammatory cytokines (so called cytokine storm) observed in patients with T2D and obesity infected with COVID-19, is a consequence of the summation and potentiation of already existing inflammatory process.


2022 ◽  
Author(s):  
Shumin Li ◽  
Siying Liu ◽  
Rui Ai Chen ◽  
Mei Huang ◽  
To Sing Fung ◽  
...  

Coronavirus infections induce the expression of multiple proinflammatory cytokines and chemokines. We have previously shown that in cells infected with gammacoronavirus infectious bronchitis virus (IBV), interleukin 6 (IL-6) and IL-8 were drastically upregulated, and the MAP kinase p38 and the integrated stress response pathways were implicated in this process. In this study, we report that coronavirus infection activates a negative regulatory loop that restricts the upregulation of a number of proinflammatory genes. As revealed by the initial transcriptomic and subsequent validation analyses, the anti-inflammatory adenine-uridine (AU)-rich element (ARE)-binding protein, Zinc finger protein 36 (ZFP36) and its related family members were upregulated in cells infected with IBV and three other coronaviruses, alphacoronaviruses porcine epidemic diarrhea virus (PEDV) and human coronavirus 229E (HCoV-229E), and betacoronavirus HCoV-OC43, respectively. Characterization of the functional roles of ZFP36 during IBV infection demonstrated that ZFP36 promoted the degradation of transcripts coding for IL-6, IL-8, dual-specificity phosphatase 1 (DUSP1), prostaglandin-endoperoxide synthase 2 (PTGS2) and TNF-α-induced protein 3 (TNFAIP3), through binding to AREs in these transcripts. Consistently, knockdown and inhibition of JNK and p38 kinase activities reduced the expression of ZFP36, as well as the expression of IL-6 and IL-8. On the contrary, overexpression of mitogen-activated protein kinase kinase 3 (MKK3) and MAPKAP kinase-2 (MK2), the upstream and downstream kinases of p38, respectively, increased the expression of ZFP36 and decreased the expression of IL-8. Taken together, this study reveals an important regulatory role of the MKK3-p38-MK2-ZFP36 axis in coronavirus infection-induced proinflammatory response. Importance Excessive and uncontrolled induction and release of proinflammatory cytokines and chemokines, the so-called cytokine release syndrome (CRS), would cause life-threatening complications and multiple organ failure in severe coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19. This study reveals that coronavirus infection also induces the expression of ZFP36, an anti-inflammatory ARE-binding protein, promoting the degradation of ARE-containing transcripts coding for IL-6 and IL-8 as well as a number of other proteins related to inflammatory response. Furthermore, the p38 MAP kinase, its upstream kinase MKK3 and downstream kinase MK2 were shown to play a regulatory role in upregulation of ZFP36 during coronavirus infection cycles. This MKK3-p38-MK2-ZFP36 axis would constitute a potential therapeutic target for severe coronavirus infections.


2003 ◽  
Vol 47 (11) ◽  
pp. 3630-3633 ◽  
Author(s):  
Teresa Krakauer ◽  
Marilyn Buckley

ABSTRACT Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). Doxycycline inhibited SE-stimulated T-cell proliferation and production of cytokines and chemokines by human peripheral blood mononuclear cells. These results suggest that the antibiotic doxycycline has anti-inflammatory effects and is therapeutically useful for mitigating the pathogenic effects of SE.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Han-Sol Lee ◽  
Jin-Hyub Paik ◽  
Ok-Kyoung Kwon ◽  
Imam Paryanto ◽  
Prasetyawan Yuniato ◽  
...  

Ethnopharmacological Relevance. Atopic dermatitis is a chronic inflammatory skin disease. Lagerstroemia ovalifolia Teijsm. & Binn. (LO) has traditionally been used as an herbal medicine for anti-inflammatory diseases. The effect of LO on atopic dermatitis has not been verified scientifically. We investigated the effects of CHCl3 fraction number 5 of LO (LOC) on atopic dermatitis through cell-based experiments. HaCaT cells were treated with tumor necrosis factor-alpha (TNFα)/interferon-gamma (IFNγ) to induce an inflammatory reaction. Proinflammatory cytokines, interleukin- (IL-) 6, IL-8, and IL-1β and chemokines such as thymus and activation-regulated chemokine (TARC/CCL17), monocyte chemoattractant protein 1 (MCP1/CCL2), and macrophage-derived chemokine (MDC/CCL22) were measured by RT-PCR and ELISA. In addition, the degree of phosphorylation and activation of JAK/STAT1, PI3K/AKT, and nuclear factor-kappa B (NF-κB) were measured by western blot and luciferase assays. The production of inflammatory cytokines and chemokines and activation of the JAK/STAT1, PI3K/AKT, and NF-κB pathways were induced by TNFα/IFNγ in HaCaT cells. Under these conditions, LOC treatment inhibited the production of targeted cytokines and chemokines and decreased the phosphorylation and activation of JAK/STAT1, PI3K/AKT, and NF-κB. These results suggest that LOC reduces the production of proinflammatory cytokines and chemokines by suppressing the JAK/STAT1, PI3K/AKT, and NF-κB pathways. Therefore, LOC may have potential as a drug for atopic dermatitis.


1993 ◽  
pp. 297-304
Author(s):  
J. J. Oppenheim ◽  
J.-M. Wang ◽  
A. W. Lloyd ◽  
D. D. Taub ◽  
D. J. Kelvin ◽  
...  

2019 ◽  
Vol 47 (9) ◽  
pp. 2174-2187 ◽  
Author(s):  
Connor G. Ziegler ◽  
Rachel Van Sloun ◽  
Sabrina Gonzalez ◽  
Kaitlyn E. Whitney ◽  
Nicholas N. DePhillipo ◽  
...  

Background: Platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are orthobiologic therapies with numerous growth factors and other bioactive molecules. Before the clinical utility of PRP and BMC is optimized as a combined therapy or monotherapy, an improved understanding of the components and respective concentrations is necessary. Purpose: To prospectively measure and compare anabolic, anti-inflammatory, and proinflammatory growth factors, cytokines, and chemokines in bone marrow aspirate (BMA), BMC, whole blood, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) from samples collected and processed concurrently on the same day from patients presenting for elective knee surgery. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients presenting for elective knee surgery were prospectively enrolled over a 3-week period. Whole blood from peripheral venous draw and BMA from the posterior iliac crest were immediately processed via centrifugation and manual extraction methods to prepare LR-PRP, LP-PRP, and BMC samples, respectively. BMA, BMC, whole blood, LR-PRP, and LP-PRP samples were immediately assayed and analyzed to measure protein concentrations. Results: BMC had a significantly higher interleukin 1 receptor antagonist (IL-1Ra) concentration than all other preparations (all P < .0009). LR-PRP also had a significantly higher IL-1Ra concentration than LP-PRP ( P = .0006). There were no significant differences in IL-1Ra concentration based on age, sex, body mass index, or chronicity of injury in all preparations. LR-PRP had significantly higher concentrations of platelet-derived growth factor AA (PDGF-AA) and PDGF-AB/BB than all other preparations (all P < .0006). LR-PRP also had significantly higher concentrations of matrix metalloproteinase 1 (MMP-1) and soluble CD40 ligand than all other preparations (all P < .004). LP-PRP had significantly higher concentrations of MMPs, namely MMP-2, MMP-3, and MMP-12, than all other preparations (all P < .007). Conclusion: BMC is a clinically relevant source of anti-inflammatory biologic therapy that may be more effective in treating osteoarthritis and for use as an intra-articular biologic source for augmented healing in the postsurgical inflammatory and healing phases, owing to its significantly higher concentration of IL-1Ra as compared with LR-PRP and LP-PRP. Additionally, LR-PRP had a significantly higher concentration of IL-1Ra than LP-PRP. In cases where increased vascularity and healing are desired for pathological or injured tissues, including muscle and tendon, LR-PRP may be optimal given its higher overall concentrations of PDGF, TGF-β, EGF, VEGF, and soluble CD40 ligand.


2013 ◽  
Vol 18 (5) ◽  
pp. 33-37
Author(s):  
O. P Popova ◽  
I. M Fedorova ◽  
S. I Koteleva

Comparative analysis of cytokine profile was performed in 149 children aged 1.5 to 14 years, out of which 41 had suffered from pertussis as monoinfection, 53 -in combination with mycoplasma infection, 55 - with acute viral infections. Cytokine profile in patients with pertussis differs in reduction of induced production of proinflammatory cytokines, especially IFN-y. A key feature of the functioning of the cytokine network in pertussis is the active production of anti-inflammatory cytokines - IL-4 and IL-10 upward the early periods of the disease, that indicates the importance of Th-2-type response in whooping cough.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Onkar P. Kulkarni ◽  
Julia Lichtnekert ◽  
Hans-Joachim Anders ◽  
Shrikant R. Mulay

Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of “proinflammatory” cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine “inflammation”? In this review, we discuss the functions of “inflammatory” mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Anh Thu Nguyen ◽  
Ki-young Kim

Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.


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