Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach

Helicobacter pylori is the most common gastric pathogen. H. pylori is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. H. pylori can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. Helicobacte...

Full description

Saved in:
Bibliographic Details
Main Authors: Licínia Santos, Sinan Sharba, John Benktander, Stefany Ojaimi Loibman, Macarena P. Quintana-Hayashi, Mattias Erhardsson, Sara K. Lindén
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Virulence
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2025.2530173
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1839627403986468864
author Licínia Santos
Sinan Sharba
John Benktander
Stefany Ojaimi Loibman
Macarena P. Quintana-Hayashi
Mattias Erhardsson
Sara K. Lindén
author_facet Licínia Santos
Sinan Sharba
John Benktander
Stefany Ojaimi Loibman
Macarena P. Quintana-Hayashi
Mattias Erhardsson
Sara K. Lindén
author_sort Licínia Santos
collection DOAJ
description Helicobacter pylori is the most common gastric pathogen. H. pylori is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. H. pylori can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. Helicobacter species infections impair the mucus barrier by decreasing the binding ability of the mucins, decreasing the growth-limiting activity of mucins and decreasing mucin production. The current study aimed to restore mucin production in the male C57BL/6 mouse H. pylori (SS1) infection model and evaluate its effects on H. pylori density. Mice infected with SS1 were treated with (R)-α-methylhistamine (RαMH) or interleukin-4 (IL4). Treatment with RαMH or IL4 restored mucin production and decreased gastric H. pylori density compared to mock-treated infected mice. Treatment with RαMH and IL4 did not affect serum anti-H. pylori IgG levels, expression of antimicrobial peptides or H. pylori virulence factors. Further, RαMH did not have cytotoxic effects on H. pylori. However, the expression of cytokines (Tnf and Il4), factors related to mucus production (Tff1, Spedf, Stat6, and Ptgs1), and mucin O-glycan sialylation levels differed between mice treated with RαMH and IL4. This suggests that increased mucus production can have similar effects on pathogen density in spite of differences in the local niche. In conclusion, agents that stimulate mucin production in the gastric mucosa have the potential to aid in the removal of pathogens from the gastric niche.
format Article
id doaj-art-f36c47e9c8e54e5c94f379e25d40f76d
institution Matheson Library
issn 2150-5594
2150-5608
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series Virulence
spelling doaj-art-f36c47e9c8e54e5c94f379e25d40f76d2025-07-16T12:40:14ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2530173Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomachLicínia Santos0Sinan Sharba1John Benktander2Stefany Ojaimi Loibman3Macarena P. Quintana-Hayashi4Mattias Erhardsson5Sara K. Lindén6Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenHelicobacter pylori is the most common gastric pathogen. H. pylori is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. H. pylori can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. Helicobacter species infections impair the mucus barrier by decreasing the binding ability of the mucins, decreasing the growth-limiting activity of mucins and decreasing mucin production. The current study aimed to restore mucin production in the male C57BL/6 mouse H. pylori (SS1) infection model and evaluate its effects on H. pylori density. Mice infected with SS1 were treated with (R)-α-methylhistamine (RαMH) or interleukin-4 (IL4). Treatment with RαMH or IL4 restored mucin production and decreased gastric H. pylori density compared to mock-treated infected mice. Treatment with RαMH and IL4 did not affect serum anti-H. pylori IgG levels, expression of antimicrobial peptides or H. pylori virulence factors. Further, RαMH did not have cytotoxic effects on H. pylori. However, the expression of cytokines (Tnf and Il4), factors related to mucus production (Tff1, Spedf, Stat6, and Ptgs1), and mucin O-glycan sialylation levels differed between mice treated with RαMH and IL4. This suggests that increased mucus production can have similar effects on pathogen density in spite of differences in the local niche. In conclusion, agents that stimulate mucin production in the gastric mucosa have the potential to aid in the removal of pathogens from the gastric niche.https://www.tandfonline.com/doi/10.1080/21505594.2025.2530173H. pylorimucinmucusstomachmouse
spellingShingle Licínia Santos
Sinan Sharba
John Benktander
Stefany Ojaimi Loibman
Macarena P. Quintana-Hayashi
Mattias Erhardsson
Sara K. Lindén
Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
Virulence
H. pylori
mucin
mucus
stomach
mouse
title Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
title_full Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
title_fullStr Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
title_full_unstemmed Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
title_short Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases Helicobacter pylori density in the murine stomach
title_sort treatment with r α methylhistamine or il4 stimulates mucin production and decreases helicobacter pylori density in the murine stomach
topic H. pylori
mucin
mucus
stomach
mouse
url https://www.tandfonline.com/doi/10.1080/21505594.2025.2530173
work_keys_str_mv AT liciniasantos treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT sinansharba treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT johnbenktander treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT stefanyojaimiloibman treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT macarenapquintanahayashi treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT mattiaserhardsson treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach
AT saraklinden treatmentwithramethylhistamineoril4stimulatesmucinproductionanddecreaseshelicobacterpyloridensityinthemurinestomach