Trial reportThe Journal of biological chemistry2014
Low molecular weight hyaluronan activates cytosolic phospholipase A2α and eicosanoid production in monocytes and macrophages.
Trial report in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- Article
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Hyaluronic Acid-like Skin Plumping and Radiance Benefits of aMarine drugs · 2026Article
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Synovial immune control failure in osteoarthritis: from maintenance of tissue homeostasis to inflammatory niche formation.Frontiers in immunology · 2026Review
- Hyaluronidase treatment is associated with increased cytokine levels and reduced peritoneal neutrophil accumulation during LPS-induced inflammation.Frontiers in pharmacology · 2026Article
- Antimicrobial Activity Versus Virulence Potential of Hyaluronic Acid: Balancing Advantages and Disadvantages.International journal of molecular sciences · 2025Review
- Metastasis-promoting functions of myeloid cells.Cancer metastasis reviews · 2025Review
- Blood-based HYAL2 methylation as a potential marker for the preclinical detection of coronary heart disease and stroke.Clinical epigenetics · 2024Article
- Role of Hyaluronic acid and its chemical derivatives in immunity during homeostasis, cancer and tissue regeneration.Seminars in immunopathology · 2024Review
- The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair.The American journal of pathology · 2024Article
- Review
- The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.Journal of cellular and molecular medicine · 2024Article
- Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation.International journal of molecular sciences · 2024Article
- Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.Frontiers in immunology · 2024Review
- Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.Sleep and biological rhythms · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- 'Two-faces' of hyaluronan, a dynamic barometer of disease progression in tumor microenvironment.Discover oncology · 2023Review
- Tissue Slice Culture and Analysis of Tumor-Associated Hyaluronan in Urothelial Carcinoma.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Hyaluronan breakdown by snake venom hyaluronidases: From toxins delivery to immunopathology.Frontiers in immunology · 2023Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix. During inflammation, there is an increased breakdown of HA, resulting in the accumulation of low molecular weight (LMW) HA and activation of monocytes and macrophages. Eicosanoids, derived from the cytosolic phospholipase A2 group IVA (cPLA2α) activation, are potent lipid mediators also attributed to acute and chronic inflammation. The aim of this study was to determine the effect of LMW HA on cPLA2α activation, arachidonic acid (AA) release, and subsequent eicosanoid production and to examine the receptors and downstream mechanisms involved in these processes in monocytes and differently polarized macrophages. LMW HA was a potent stimulant of AA release in a time- and dose-dependent manner, induced cPLA2α, ERK1/2, p38, and JNK phosphorylation, as well as activated COX2 expression and prostaglandin (PG) E2 production in primary human monocytes, murine RAW 264.7, and wild-type bone marrow-derived macrophages. Specific cPLA2α inhibitor blocked HA-induced AA release and PGE2 production in all of these cells. Using CD44, TLR4, TLR2, MYD88, RHAMM or STAB2 siRNA-transfected macrophages and monocytes, we found that AA release, cPLA2α, ERK1/2, p38, and JNK phosphorylation, COX2 expression, and PGE2 production were activated by LMW HA through a TLR4/MYD88 pathway. Likewise, PGE2 production and COX2 expression were blocked in Tlr4(-/-) and Myd88(-/-) mice, but not in Cd44(-/-) mice, after LMW HA stimulation. Moreover, we demonstrated that LMW HA activated the M1 macrophage phenotype with the unique cPLA2α/COX2(high) and COX1/ALOX15/ALOX5/LTA4H(low) gene and PGE2/PGD2/15-HETE(high) and LXA4(low) eicosanoid profile. These findings reveal a novel link between HA-mediated inflammation and lipid metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.