scholarly journals Chemokine and Cytokine Profiles in Patients with Hand Osteoarthritis

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Jiří Baloun ◽  
Tereza Kropáčková ◽  
Hana Hulejová ◽  
Michal Tomčík ◽  
Olga Růžičková ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Hand Osteoarthritis ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Ultrasound Findings ◽  
Linear Modelling ◽  
Small Hand ◽  
Healthy Control ◽  
Necrosis Factor ◽  
Human Cytokine

Background: The development of hand osteoarthritis (HOA) and its progression into the erosive subset are unclear, but inflammation is suspected to be the main source. To verify the involvement of inflammation in HOA pathogenesis, we evaluate serum inflammatory mediators and their association with HOA-related clinical features in patients. Methods: 153 participants (50 non-erosive HOA patients, 54 erosive HOA patients, and 49 healthy control subjects) were included in this study. All patients underwent clinical examination, which included assessment of tender and swollen small hand joints, ultrasound (US) examination, and self-reported measures (e.g., AUSCAN or algofunctional indexes). Serum inflammatory mediators were quantified using human cytokine 27-plex immunoassay. We employed linear modelling, correlation analysis, and resampling statistics to evaluate the association of these mediators to HOA. Results: We identified increased levels of nine inflammatory mediators (e.g., eotaxin, monocyte chemoattractant protein 1, interleukin-8, and tumour necrosis factor) in HOA patients compared to healthy controls. Increased mediators correlated with ultrasound findings as well as with clinically tender and swollen joint counts in patients with erosive HOA. However, none of the mediators distinguished between erosive and non-erosive HOA subtypes. Conclusion: Our findings support the hypothesis on the involvement of inflammation in HOA.

The MKK6/p38 Stress Kinase Cascade Is Critical for Tumor Necrosis Factor-–Induced Expression of Monocyte-Chemoattractant Protein-1 in Endothelial Cells

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 857-865 ◽  
Author(s):  
Matthias Goebeler ◽  
Karin Kilian ◽  
Reinhard Gillitzer ◽  
Manfred Kunz ◽  
Teizo Yoshimura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Dominant Negative ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Kinase Cascade ◽  
Stress Kinase ◽  
Necrosis Factor

Abstract Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C subfamily of chemokines, is important for the local recruitment of leukocytes to sites of inflammatory challenge. Here, we investigated endothelial signaling pathways involving members of the mitogen-activated protein (MAP) kinase superfamily and studied their role for MCP-1 expression in endothelium. We show that tumor necrosis factor- (TNF-), a potent inflammatory activator of endothelium, leads to activation of MAP kinases ERK, p38, and JNK in human umbilical vein endothelial cells (HUVEC). Contribution of MAP kinase pathways to TNF-–induced synthesis of endothelial MCP-1 was then studied by pharmacologic inhibition and transient expression of dominant negative or constitutively active kinase mutants using flow cytometry, Northern blot, and luciferase reporter gene assays. Inhibition of Raf/MEK/ERK or SEK/JNK pathways had no significant effect on MCP-1 levels, whereas blocking the MKK6/p38 pathway by p38 inhibitors SB203580 or SB202190 or by a dominant negative mutant of MKK6, the upstream activator of p38, strongly inhibited TNF-–induced expression of MCP-1. Consistent with that finding, expression of wild-type or constitutively active MKK6 significantly enhanced the effect of limiting TNF- concentrations on MCP-1 synthesis. These data suggest a crucial role for the MKK6/p38 stress kinase cascade in TNF-–mediated endothelial MCP-1 expression.

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