rss
Ann Rheum Dis 70:2052-2054 doi:10.1136/ard.2010.145672
  • Letters

Adiponectin and leptin increase IL-8 production in human chondrocytes

  1. Oreste Gualillo1
  1. 1SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, Santiago de Compostela, Spain
  2. 2SERGAS, Research Laboratory 7, Molecular and Cellular Cardiology, Institute of Medical Research (IDIS), Santiago University Clinical Hospital, Santiago de Compostela, Spain
  1. Correspondence to Dr Oreste Gualillo, SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, Travesia Choupana s/n, Building C, Level -2, Santiago de Compostela 15706, Spain; oreste.gualillo{at}sergas.es
  1. Contributors RG participated in acquisition of data, analysis and interpretation of data and critical revision of the manuscript. MS and JC participated in acquisition of data, drafting of the manuscript and statistical analysis. JJG-R participated in analysis and interpretation of data and drafting of the manuscript. FL participated in analysis and interpretation of data, critical revision of the manuscript and scientific supervision of experiments. OG participated in conception and design of the study, in analysis and interpretation of data, critical revision of the manuscript and scientific supervision of experiments.

  • Accepted 23 April 2011
  • Published Online First 29 May 2011

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two of the most frequent articular diseases. Recently, adipokines have been proposed as relevant mediators of cartilage degeneration in both OA and RA.1 Our group has previously demonstrated that RA patients have elevated serum levels of leptin and adiponectin,2 while others have shown positive associations between serum levels of leptin and hip-radiographic OA,3 and of adiponectin and erosive OA.4 Thus, several studies have suggested that adipokines can modulate the pattern of cytokine production towards a pro-inflammatory state. We have also demonstrated that leptin and adiponectin, the two most prominent members of the adipokine superfamily, contribute significantly to cartilage damage, due to their ability to induce nitric oxide (NO), pro-inflammatory cytokines and matrix metalloproteinases (MMPs).5

Interleukin 8 (IL-8) is a pro-inflammatory CXC chemokine associated with neutrophils, T cells, basophils and macrophage chemotaxis. Increased IL-8 expression has been found in the cells of the synovial lining in both OA and RA.6 Indeed, it has been reported that in both pathologies, the pannus has a similar pattern of IL-8 secretion.7 IL-8 expression, moreover, has been suggested to contribute to aggressive synovitis in psoriatic arthritis8 and be localised to the foci of chondrocyte hypertrophy that frequently develop in OA cartilage, which can promote dysregulated matrix repair and pathological calcification.9

Together with the evidence that human chondrocytes express both IL-8 receptors,9 we were therefore prompted to study the role of adiponectin and leptin on expression of IL-8 in human cultured chondrocytes. Using quantitative real-time PCR and ELISA assays, we demonstrate that both adipokines induce IL-8 mRNA synthesis and protein secretion by human cultured chondrocytes, thus revealing a novel pro-inflammatory role for adiponectin and leptin within the joint tissue.

Using doses selected on the basis of published studies, treatment of primary cultured human chondrocytes with 10 μg/ml adiponectin (figure 1A) or 800 nM leptin (figure 1B) induced a highly significant increase in IL-8 mRNA levels. Both adipokine treatments also induced IL-8 protein levels in the culture supernatant of the primary human chondrocytes (figure 1C,D). In our hands, adiponectin was able to induce IL-8 secretion more strongly than that of IL-1β (data not shown).

Figure 1

(A and B) Human interleukin 8 (IL-8) expression determined by quantitative real-time PCR after treatment with adiponectin and leptin during 48 h in serum free medium (DMEM F12). (C and D) Human IL-8 secretion determined by ELISA in the supernatant of human primary chondrocytes treated with adiponectin and leptin during 48 h in serum free medium (DMEM F12). Data are represented as mean±SEM of at least three independent experiments. Each observation was made in triplicate. **p<0.01, ***p<0.001 (analysis of variance+post-hoc test: Bonferroni multiple comparison test).

Our data are in agreement with a recent study showing that leptin and adiponectin can increase IL-8 expression in human synovial fibroblasts.10 Taken together, these results depict a scenario in which both adipokines enhance the chemotactic environment in the joint.

The infrapatellar fat pad has been suggested as an in vivo intra-articular source of adipokines and is indeed becoming recognised as an active joint tissue.11 It would therefore be reasonable to hypothesise that increased adipokine secretion by the infrapatellar fat pad in obese OA patients contributes to damage of the adjacent cartilage, which in turn leads to increased NO, MMP and IL-8 production.5 Moreover, because human chondrocytes express receptors for IL-8, adiponectin and leptin, as well as the factors themselves, it is also possible that IL-8 secretion induced by these adipokines also has an autocrine function.

In conclusion, in the current study we have demonstrated that leptin and adiponectin induce IL-8 secretion in human primary chondrocytes. These results corroborate our previous data showing that in cartilage adiponectin and leptin have a pro-inflammatory role, increasing IL-8 levels and thus contributing significantly to the chemotactic gradient seen in inflamed joints.

Acknowledgments

The authors gratefully acknowledge the expert technical assistance of Veronica Lopez.

Footnotes

  • Funding The work of OG and FL is funded by Instituto de Salud Carlos III and Xunta de Galicia (SERGAS) through a research-staff stabilisation contract. They are supported by Instituto de Salud Carlos III and Xunta de Galicia (OG grants: PI08/0040 and PGIDIT07PXIB918090PR; FL grants: PI060919, PI08/0044 and PGIDIT06PXIB918307PR). This work was also partially supported by the RETICS Programme, RD08/0075 (RIER) and REDINSCOR via Instituto de Salud Carlos III (ISCIII), within the VI NP of R+D+I 2008–2011.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Santiago University Clinical Hospital Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

References