Digestive Diseases and Sciences

, Volume 49, Issue 9, pp 1526–1530 | Cite as

Structural Signaling Regulates Inflammation-Induced Enhanced Restitution and Increased Mib-1 and Bax-Indexes After Superficial Injury in Isolated Guinea Pig Gastric Mucosa

  • Arun C. Bhowmik
  • Niku K. I. Oksala
  • Jukka P. Auriko
  • Timo Paavonen
  • Harri Mustonen
  • Hannu Paimela


Several growth factors and cytokines are involved in regulation of the immediate repair of gastrointestinal mucosa, a process also called restitution. Few data exist on the effect of inflammation on this process using an explant model, where the folded basal lamina is included. The aim of the present study was to investigate the effect of simulated inflammation on restitution and on concomitant proliferation and apoptosis in isolated guinea pig gastric mucosa. Paired gastric mucosae were mounted in Ussing chambers (37°C) and a superficial injury was induced (1.25 M NaCl/5 min) followed by a 4-hr restitution (pH 7.3–7.5). During perfusion, simulated inflammation was induced (with 0.5 or 5.0 ng/ml IL-1β or with activated polymorphonuclear [PMN] cells). The PI (proliferative index) and AI (apoptotic index) are expressed as the number of Mib-1- or Bax-immunopositive cells per 300 foveolar cells, respectively. The mean recovery of electrophysiological resistance of tissues (R) after injury and exposure to serosal IL-1β during restitution was 95.2 ± 5.3% (mean ± SD), whereas the value for control tissues was 89.6 ± 6.9% (P=0.016; N=9). The mean recovery of R in tissues exposured to activated serosal PMN cells during restitution was 97.6 ± 2.7%, whereas the value for unexposed control tissues was 93.8 ± 2.9 (P=0.004; N=9). The enhancing effect of PMN cells was partially eliminated by serosal anti-ICAM, whereas serosal cytochalasin D abolished the process completely. The PI of tissues exposed to serosal PMN cells was 34.6 ± 17.3, whereas the value for unexposed controls was 24.7 ± 15.5 (P=0.04; N=5). The corresponding AI values were 17.0 ± 2.8 and 12.0 ± 5.7, respectively (NS; N=4). Simulated inflammation either with serosal IL-1β or with activated PMN cells enhances restitution and proliferation, whereas their effect on AI is only suggestive. Exogenous serosal anti-ICAM modulates restitution, whereas cytochalasin D abolishes it completely, suggesting that the structural signaling system including focal adhesions and cytoskeleton plays a significant role in the regulation of restitution.

apoptosis cell signaling epithelial repair inflammation proliferation restitution 


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Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Arun C. Bhowmik
    • 1
  • Niku K. I. Oksala
    • 2
    • 3
  • Jukka P. Auriko
    • 1
  • Timo Paavonen
    • 4
  • Harri Mustonen
    • 1
  • Hannu Paimela
    • 1
  1. 1.Department of SurgeryHelsinki University Central Hospital, Jorvi HospitalEspooFinland
  2. 2.Department of Vascular SurgeryTampere University Central HospitalTampereFinland
  3. 3.Medical School, PathologyTampere UniversityTampereFinland
  4. 4.Departments of PathologyUniversity of Helsinki and Oulu, and Haartman Institute, University of HelsinkiFinland

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