Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria.
Bacterial infection of the lung is associated with mucin overproduction. In partial explanation of this phenomenon, we recently reported that supernatant from the Gram-negative organism Pseudomonas (P.) aeruginosa contained an activity that upregulated transcription of the MUC 2 mucin gene [J.-D. Li, A. Dohrman, M. Gallup, S. Miyata, J. Gum, Y. Kim, J. Nadel, A. Prince, C. Basbaum, Transcriptional activation of mucin by P. aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease, Proc. Natl. Acad. Sci. U.S.A., 94 (1997) 967-972]. The purpose of the present study was to determine whether mucin genes other than MUC 2 are so regulated and whether Gram-positive organisms also contain mucin stimulatory activity. Results from in situ hybridization and RNase protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2 in both bronchial explants and cultured airway epithelial cells. The upregulation of both genes by P. aeruginosa can be mimicked by lipopolysaccharide (LPS) and can be blocked by the tyrosine kinase inhibitor genistein. In addition, both genes are upregulated by a variety of Gram-positive as well as Gram-negative organisms showing the same rank order of potency. These data indicate the existence of a general mechanism by which epithelial cells respond to the presence of bacteria by increasing mucin synthesis.
Dohrman
A
A
Department of Anatomy, University of California San Francisco, San Francisco CA 94143, USA.
Miyata
S
S
Gallup
M
M
Li
J D
JD
Chapelin
C
C
Coste
A
A
Escudier
E
E
Nadel
J
J
Basbaum
C
C
D001980:Bronchi / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D003470:Culture Media; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D005786:Gene Expression Regulation; D006090:Gram-Negative Bacteria / Q000254:growth & development / Q000502:physiology*; D006094:Gram-Positive Bacteria / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics*; D009924:Organ Culture Techniques; D011549:Pseudomonas / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000502:physiology; D013297:Streptococcus pyogenes / Q000502:physiology; D015854:Up-Regulation
D003470:Culture Media; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger