Brevenal, a Marine Natural Product, is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells

• Published in: Marine drugs 2019-03, Vol.17 (3), p.184
• Main Authors: Keeler, Devon M, Grandal, Meghan K, McCall, Jennifer R
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammatory; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Aquatic Organisms - chemistry; Asthma; Bacterial diseases; brevenal; Cell activation; Cell Line, Tumor; Cell surface; chemokine; Chemokines; Chronic Disease - therapy; Chronic obstructive pulmonary disease; COPD; Cystic fibrosis; cytokine; Cytokines; Dinoflagellida - chemistry; Disease; Drug development; Drug Evaluation, Preclinical; Drugs; Epithelial cells; Epithelial Cells - drug effects; Epithelium; Ethers - pharmacology; Ethers - therapeutic use; Genotype & phenotype; Humans; Immune system; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Immunomodulation; immunomodulator; Immunomodulators; Inflammation; Investigations; Lipopolysaccharides; Lung - cytology; Lung diseases; Lungs; macrophage activation; macrophage phenotype; Macrophages; Macrophages - drug effects; marine natural product; Mice; mucociliary clearance; Mucus; Natural products; Neutrophils; Obstructive lung disease; Phenotypes; Polymers - pharmacology; Polymers - therapeutic use; Population; Respiratory diseases; Respiratory Mucosa - cytology; Respiratory Tract Diseases - drug therapy; Respiratory Tract Diseases - immunology; Secretion; TLR4 protein; Toll-like receptors
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17030184

Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are some of the leading causes of illness and fatalities worldwide. The search for novel treatments led to the exploration of marine natural products as drug candidates to combat the debilitating effects of mucus accumulation and chronic inflammation. Previous research showed that an alga-derived compound, brevenal, could attenuate the effects of inflammatory agents, but the mechanisms by which it exerted its effects remained unclear. We investigated the effects of brevenal on lipopolysaccharide (LPS) induced cytokine/chemokine production from murine macrophages and human lung epithelial cells. It was found that brevenal reduces proinflammatory mediator secretion while preserving anti-inflammatory secretion from these cells. Furthermore, we found that brevenal does not alter cell surface Toll-like receptor 4 (TLR4) expression, thereby maintaining the cells' ability to respond to bacterial infection. However, brevenal does alter macrophage activation states, as demonstrated by reduced expression of both M1 and M2 phenotype markers, indicating this putative anti-inflammatory drug shifts innate immune cells to a less active state. Such a mechanism of action would be ideal for reducing inflammation in the lung, especially with patients suffering from chronic respiratory diseases, where inflammation can be lethal.