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

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.

• Authors: Kazuhiro Tange, Sen Yagi, Eiji Takeshita, Masanori Abe, Yasunori Yamamoto, Hideomi Tomida, Tomoe Kawamura, Masakazu Hanayama, Bunzo Matsuura, Yoshiou Ikeda, Yoichi Hiasa
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 17983 (10 26 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 36289244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

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

Topics

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