Oral administration of human carbonic anhydrase I suppresses colitis in a murine inflammatory bowel disease model

Sci Rep. 2022 Oct 26;12(1):17983. doi: 10.1038/s41598-022-22455-y.

Abstract

The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (RORγt) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-γ) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Carbonic Anhydrase I
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Disease Models, Animal
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Interferon-gamma / therapeutic use
  • Interleukin-17
  • Interleukin-6 / therapeutic use
  • Mesalamine / therapeutic use
  • Mice
  • Mice, SCID
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phosphates / therapeutic use
  • Prednisolone / therapeutic use
  • Tretinoin / therapeutic use

Substances

  • Interleukin-17
  • Carbonic Anhydrase I
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Interferon-gamma
  • Interleukin-6
  • Mesalamine
  • Prednisolone
  • Tretinoin
  • Phosphates