Neutrophil Elastase and Interleukin 17 Expressed in the Pig Colon during Brachyspira hyodysenteriae Infection Synergistically with the Pathogen Induce Increased Mucus Transport Speed and Production via Mitogen-Activated Protein Kinase 3

• Brachyspira hyodysenteriae colonizes the pig colon, resulting in mucoid hemorrhagic diarrhea and mucus layer changes. These changes are characterized by a disorganized mucus structure and massive mucus induction with de novo expression of MUC5AC and increased production of MUC2. To investigate the mechanisms behind this altered mucin environment, we quantified the mRNA levels of mucin pathway genes and factors from the immune system in the colons of infected and control pigs and observed upregulation of neutrophil elastase, SPDEF, FOXA3, MAPK3/ ERK1, IL-17A, IL-1 beta, IL-6, and IL-8 expression. In vitro, colonic mucus-producing mucosal surfaces were treated with these factors along with B. hyodysenteriae infection and analyzed for their effect on mucin production. Neutrophil elastase and infection synergistically induced mucus production and transport speed, and interleukin 17A (IL-17A) also had similar effects, in both the presence and absence of infection. A mitogen-activated protein kinase 3 (MAPK3)/extracellular signal-regulated kinase 1 (ERK1) inhibitor suppressed these effects. Therefore, we suggest that the SPDEF, FOXA3, and MAPK3/ERK1 signaling pathways are behind the transcriptional program regulating mucin biosynthesis in the colon during B. hyodysenteriae infection. In addition to furthering the knowledge on this economically important disease, this mechanism may be useful for the development of therapies aimed at conditions where enhancing mucus production may be beneficial, such as chronic inflammatory disorders of the colon.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Nyckelord

cytokine

goblet cell

mucus

spirochete

swine

pro-inflammatory cytokines

messenger-rna expression

o-linked

glycosylation

mucin gene-expression

tumor-necrosis-factor

epithelial-cells

antimicrobial susceptibility

serpulina-hyodysenteriae

bacterial pathogens

intestinal mucus

Immunology

Infectious Diseases

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