title: Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?
abstract: 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.
authors.affiliation: Research Center for Endocrinology and Metabolism, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hägg
authors.forename: Sara
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
authors.forename: Annika
authors.initials: A
authors.lastname: Rosengren
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.forename: Alexandra
authors.initials: A
authors.lastname: Krettek
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D003327:Coronary Disease / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005246:Feedback; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D018960:Hyaluronan Receptors; D015850:Interleukin-6