Cystic fibrosis (CF) is characterized by progressive airway obstruction. Although it has been postulated that this is due in part to mucus hypersecretion, there are no published data showing an increase in the gel-forming mucins MUC5AC or MUC5B in CF secretions. We used confocal microscopy to assess the amount of mucin-like glycoprotein and DNA in CF sputum and found more mucin in bronchitis sputum and a much greater amount of DNA in CF sputum. We then used antibodies to MUC5AC and MUC5B with Western gels and dot-blot to quantify mucin in sputum from 12 patients with CF and 11 subjects without lung disease. There was a 70% decrease in MUC5B and a 93% decrease in MUC5AC in CF sputum (P < 0.005 for both). We conclude that the vol/vol concentration of MUC5AC and MUC5B are decreased in the CF airways relative to normal mucus. This may be due to a relative increase in other components of sputum in the CF airway or to a primary defect in mucin secretion in CF.
The corticotropin-releasing factor (CRF) 3 receptor family is involved in the regulation of the hypothalamic-pituitary-adrenal stress axis in mammals (1-3). A large body of evidence points to a major role of the receptors in mediating CRF effects in anxiety and depressive disorders and in stress-associated pathologies. Two types of CRF receptors are known, the CRF 1 and the CRF 2 receptors. The CRF 1 receptor is expressed mainly in the pituitary and central nervous system and binds CRF with high affinity. It mediates adrenocorticotrophic hormone release from the anterior pituitary and is involved in the endocrine, autonomic, and cognitive responses to stress stimuli. The CRF 2 receptors are expressed in the central nervous system but also in the periphery including skeletal muscle cells, cardiac myocytes, and cells of the gastrointestinal tract. Three splice variants of CRF 2 receptors have been described: CRF 2(a) , CRF 2(b) , and CRF 2(c) receptors. They bind CRF with low and the urocortins 1-3 with high affinity. The CRF 2 receptors are involved in the regulation of feeding behavior (4) and in recovery from a stress response (5). It is likely that they are also involved in modulating anxiety-related behavior.The CRF receptors belong to the small subgroup of GPCRs (5-10%) possessing putative N-terminal signal peptides. These peptides are believed to be cleaved-off after mediating the ER targeting/insertion process (6, 7). The majority (90 -
Increased serum levels of the S100A8 (MRP-8) protein have been reported in inflammatory conditions including bacterial infection, arthritis, and cystic fibrosis (CF). This protein is expressed constitutively with S100A9 (MRP-14) in neutrophils and is regulated by inflammatory stimulants. It has been hypothesized that increased inflammatory response to persistent bacterial infection is a major feature of CF lung disease. Therefore, the authors wished to determine the involvement of these two proteins in the innate defense response of the bronchial epithelium to lipopolysaccharide (LPS). Human bronchial epithelial cells (16HBE14o-) and primary bronchial epithelial cells (NHBE) were grown at air-liquid interface (ALI) and stimulated for up to 96 hours with LPS from Pseudomonas aeruginosa. The 16HBE14o- cells responded to LPS with a 2.9-fold increase in S100A8 mRNA production after 12 hours. S100A9 mRNA production was increased by 1.8-fold after 12 hours and 2.9-fold after 24 hours. It was also found that the S100A8 and S100A9 proteins were increased in the secretions of the 16HBE14o- and NHBE cells after LPS stimulation. This finding suggests that S100A8 and S100A9 are involved in the innate defense of the bronchial epithelium.
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