Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation.

Abstract

Cationic host defense peptides (CHDP) are immunomodulatory molecules that control infections and contribute to immune homeostasis. CHDP such as cathelicidin and calprotectin expression is altered in the arthritic synovium, and in the lungs of asthma and COPD patients. Recent studies suggest a link between airway inflammation and the immunopathology of arthritis. Therefore, in this study we compared the abundance of mouse cathelicidin (CRAMP), defensins, and calprotectin subunits (S100A8 and S100A9) in murine models of collagen-induced arthritis (CIA) and allergen house dust mite (HDM)-challenged airway inflammation. CRAMP, S100A8, and S100A9 abundance were significantly elevated in the joint tissues of CIA mice, whereas these were decreased in the lung tissues of HDM-challenged mice, compared to naïve. We further compared the effects of administration of two different synthetic immunomodulatory peptides, IG-19 and IDR-1002, on cathelicidin and calprotectin abundance in the two models. Administration of IG-19, which controls disease progression and inflammation in CIA mice, significantly decreased CRAMP, S100A8, and S100A9 levels to baseline in the joints of the CIA mice, which correlated with the decrease in cellular influx in the joints. However, administration of IDR-1002, which suppresses HDM-induced airway inflammation, did not prevent the decrease in the levels of cathelicidin and calprotectin in the lungs of HDM-challenged mice. Cathelicidin and calprotectin levels did not correlate with leukocyte accumulation in the lungs of the HDM-challenged mice. Results of this study suggest that endogenous cathelicidin and calprotectin abundance are disparately altered, and may be differentially regulated, within local tissues in airway inflammation compared to arthritis.

• Authors: Mahadevappa Hemshekhar, Hadeesha Piyadasa, Dina Mostafa, Leola N Y Chow, Andrew J Halayko, Neeloffer Mookherjee
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 1932 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 32973796 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Hemshekhar, Piyadasa, Mostafa, Chow, Halayko and Mookherjee.

Chemical References

• Allergens
• Antigens, Dermatophagoides
• Antimicrobial Cationic Peptides
• Calgranulin A
• Calgranulin B
• Collagen Type II
• Immunologic Factors
• Leukocyte L1 Antigen Complex
• Lipopolysaccharides
• S100A9 protein, mouse
• S100a8 protein, mouse
• lipopolysaccharide, Escherichia coli O111 B4
• Cathelicidins

Topics

• Allergens
• Animals
• Antigens, Dermatophagoides
• Antimicrobial Cationic Peptides (metabolism)
• Arthritis, Experimental (chemically induced, drug therapy, immunology, metabolism)
• Asthma (chemically induced, drug therapy, immunology, metabolism)
• Calgranulin A (metabolism)
• Calgranulin B (metabolism)
• Collagen Type II
• Female
• Immunologic Factors (pharmacology)
• Joints (drug effects, immunology, metabolism)
• Leukocyte L1 Antigen Complex (metabolism)
• Leukocytes (drug effects, immunology, metabolism)
• Lipopolysaccharides
• Lung (drug effects, immunology, metabolism)
• Male
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Cathelicidins