Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cells.
OBJECTIVE
Inducible heat shock proteins (hsps), particularly hsp25 and hsp72, are expressed by surface colonocytes and may have a role in protecting intestinal epithelial cells against injury. This study is aimed at determining if enteric bacteria and/or immune signals regulate their physiologic expression.


METHODS
Intestinal hsp25, hsp72, and constitutive hsc73 expression were studied in immunodeficient RAG-1(-/-) mice and in normal mice. Mucosal permeability was measured by mannitol flux and transepithelial resistance. Hsp expression in intestinal YAMC cells was assessed after incubation with recombinant cytokines, activated lamina propria lymphocytes (LPLs), or Bacteroides fragilis.


RESULTS
Chronic metronidazole treatment decreases colonic mucosal hsp25 and hsp72 expression, an effect associated with increased susceptibility of mucosal barrier function to C. difficile toxin A. Hsp expression also was increased in YAMC cells incubated with B. fragilis, an effect mediated by lipopolysaccharide and other bacteria-derived factors. Colonic hsp72, but not hsp25 or hsc73, expression is decreased in RAG-1(-/-) mice. Recombinant IL-2 and other cytokines enhance YAMC hsp25 and/or hsp72 expression. Activated LPLs induce YAMC hsp expression, an effect blocked by IL-2 neutralizing antibody.


CONCLUSIONS
Enteric flora and mucosal lymphocytes play a role in maintaining physiologic expression of colonocyte hsp25 and hsp72.
Department of Medicine, The MArtin Boyer Laboratory, The University of Chicago, Illinois 60637, USA.
Keishi
K
Kojima
Mark W
MW
Musch
Hongyu
H
Ren
David L
DL
Boone
Barbara A
BA
Hendrickson
Averil
A
Ma
Eugene B
EB
Chang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D003106:Colon / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D004755:Enterobacteriaceae; D004768:Enterotoxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000382:microbiology / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D018106:CD28 Antigens; D017252:CD3 Complex; D004768:Enterotoxins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; C486113:Hsbp1 protein, mouse; D007376:Interleukin-2; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C041348:tcdA protein, Clostridium difficile; C064658:RAG-1 protein; D008795:Metronidazole