CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

Ren, Guomin; Al-Jezani, Nedaa; Railton, P.; Powell, James; Krawetz, Roman

doi:10.1016/j.isci.2020.101943

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…Ren et al described increased protein expression in articular chondrocytes during OA-induced cartilage damage [ 34 ]. The following studies of this group also revealed: heightened synovial fluid chemokine concentration in OA group when compared to healthy subjects, its correlation with synovitis and constricting impact of CCL22 on anti-inflammatory cytokines expression ( 33 ).…”

Section: Discussionmentioning

confidence: 93%

“…CCL22 is further described as attenuating the development and function of Tregs by inhibiting the expression of Foxp3 transcription factor in STAT5-dependent manner [ 32 ]. Its role in inflammation could be considered quite ambiguous, since this potent chemotactic molecule affects both anti- and pro-inflammatory leukocytes [ 33 ]. It was also implied that CCL22, through pro-apoptotic activity on chondrocytes, takes direct part in initiating cartilage degeneration in OA—chemokine was appointed biomarker of cartilage degeneration in OA [ 34 ] and potential biomarker of early OA [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

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Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

et al. 2022

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Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex® Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex® MAGPIX® platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls—they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

et al. 2022

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“…rhPRG4 was incubated with β1-3 galactosidase and α2-3, 6, 8 neuraminidase (New England BioLabs, Ipswich, MA, US) separately or in combination (simultaneously) according to the manufacturer’s instructions. FLSs were prepared ( Ren et al, 2021 ) from normal individuals ( n = 3) and OA patients ( n = 3) and were incubated with 15 mg of rhPRG4 (intact, deglycosylated with α2-3, 6, 8 neuraminidase, β1-3 galactosidase, or both) for 48 h at 37°C at 5% CO 2 . The effect of the deglycosylation was monitored as a shift in the migration of rhPRG4 using SDS-PAGE ( Supplementary Figure S3 ).…”

Section: Methodsmentioning

confidence: 99%

Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines

Huang

Thomsson

Jin

et al. 2022

Front. Mol. Biosci.

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The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation.

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“…According to the number and location of the highly conserved N‐terminal cysteines, chemokines are grouped into four different subfamilies: CC, CXC, CX3C, XC, and the nomenclature of the receptors is essentially similar to that of corresponding chemokines, that is, CC chemokine (CCL) binds to CC chemokine receptor (CCR) and CX3C ligand binds to CX3C receptor (CX3CR) (Table 1 ). 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 Depending on their functions in the body, chemokines are also categorized into proinflammatory c...…”

Section: Chemokine Systemsmentioning

confidence: 99%

“…According to the number and location of the highly conserved N‐terminal cysteines, chemokines are grouped into four different subfamilies: CC, CXC, CX3C, XC, and the nomenclature of the receptors is essentially similar to that of corresponding chemokines, that is, CC chemokine (CCL) binds to CC chemokine receptor (CCR) and CX3C ligand binds to CX3C receptor (CX3CR) (Table 1). 23–70 Depending on their functions in the body, chemokines are also categorized into proinflammatory chemokines, homeostatic chemokines, or chemokines with both functions. Homeostatic chemokines, such as CCL17, CXCL14, and CXCL15, are produced constitutively in lymphocytes or other organs under normal biological conditions and are crucially important for immune surveillance because they primarily govern the homeostatic migration and homing of various immune cells 71 .…”

Section: Chemokine Systemsmentioning

confidence: 99%

Role of chemokine systems in cancer and inflammatory diseases

Zhao

2022

MedComm

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Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

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CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

Cited by 11 publications

References 42 publications

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines

Role of chemokine systems in cancer and inflammatory diseases

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