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Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients
R J Rodenburg1, F H van Den Hoogen, P Barrera
1Department of Biochemistry, University of Nijmegen, The Netherlands.
Objective:
Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels.
Methods:
Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1beta (IL1beta), IL8, and alpha(2) macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).
Results:
Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1beta and alpha(2) macroglobulin mRNAs.
Conclusion:
These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.
Insights
Activated macrophages from rheumatoid arthritis (RA) patients show higher interleukin-8 (IL8) mRNA production than those from healthy individuals. This increased IL8 production is an intrinsic trait of RA macrophages, contributing to joint inflammation.
Area of Science:
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is characterized by synovial inflammation driven by activated monocytes and macrophages.
- These cells play a crucial role in RA pathogenesis and prognosis.
Purpose of the Study:
- To investigate whether monocytes and monocyte-derived macrophages from RA patients exhibit increased cytokine mRNA levels.
- Specifically examining the production of interleukin-1 beta (IL1beta), IL8, and alpha(2) macroglobulin mRNA.
Main Methods:
- Monocyte-derived macrophages from RA patients and healthy controls were cultured with or without lipopolysaccharide.
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze mRNA expression levels of GAPDH, IL1beta, IL8, and alpha(2) macroglobulin.
Main Results:
- Activated macrophages from RA patients produced significantly higher IL8 mRNA levels compared to activated macrophages from healthy controls.
- Resting RA and control macrophages showed similar IL8 mRNA levels.
- No significant differences in IL1beta and alpha(2) macroglobulin mRNA expression were observed between RA and control macrophages.
Conclusions:
- The heightened IL8 mRNA production by activated RA macrophages is an intrinsic cellular property, not influenced by circulating factors.
- This innate hyper-responsiveness of RA macrophages likely contributes to elevated IL8 levels in rheumatoid joint synovial fluid.
- This mechanism is implicated in leukocyte homing to the joints, exacerbating RA inflammation.