Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?
Artikel i vetenskaplig tidskrift, 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

Författare

Daniel Hägg

Göteborgs universitet

Sara Sjöberg

Göteborgs universitet

Lillemor Mattsson Hultén

Göteborgs universitet

Björn Fagerberg

Göteborgs universitet

Olov Wiklund

Göteborgs universitet

Annika Rosengren

Göteborgs universitet

Lena M S Carlsson

Göteborgs universitet

Jan Borén

Göteborgs universitet

Per-Arne Svensson

Göteborgs universitet

Alexandra Krettek

Göteborgs universitet

Atherosclerosis

0021-9150 (ISSN)

Vol. 190 2 291-7

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.atherosclerosis.2006.03.020

PubMed

16620830

Mer information

Skapat

2017-10-10