Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?
Journal article, 2007
The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevated levels of CD44 transcript and protein (1.5-fold) compared to matched controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic factors influence CD44 expression, two single nucleotide polymorphisms in the CD44 gene were analyzed but these were not associated with coronary artery disease. We also examined the potential connection between plasma cytokine levels and CD44 expression. In atherosclerotic subjects, elevated CD44 expression correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus 14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback loop may aggravate atherosclerosis development.
Coronary Disease/genetics/immunology
Single Nucleotide
Atherosclerosis/blood/genetics/*immunology
*Polymorphism
Reverse Transcriptase Polymerase Chain Reaction
Mice
Humans
Interleukin-6/*blood/genetics
CD44/*genetics
Nucleic Acid Hybridization
Macrophages/*immunology/pathology
Antigens
Animals
Feedback
CD/genetics/immunology
Cytokines/blood
Antigens
Oligonucleotide Array Sequence Analysis
Author
Daniel Hägg
University of Gothenburg
Sara Sjöberg
University of Gothenburg
Lillemor Mattsson Hultén
University of Gothenburg
Björn Fagerberg
University of Gothenburg
Olov Wiklund
University of Gothenburg
Annika Rosengren
University of Gothenburg
Lena M S Carlsson
University of Gothenburg
Jan Borén
University of Gothenburg
Per-Arne Svensson
University of Gothenburg
Alexandra Krettek
University of Gothenburg
Atherosclerosis
0021-9150 (ISSN) 18791484 (eISSN)
Vol. 190 2 291-7Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1016/j.atherosclerosis.2006.03.020
PubMed
16620830