TITLE

Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways

AUTHOR(S)
Schauber, J.; Svanholm, C.; Termén, S.; Iffland, K.; Menzel, T.; Scheppach, W.; Melcher, R.; Agerberth, B.; Lührs, H.; Gudmundsson, G.H.
PUB. DATE
May 2003
SOURCE
Gut;May2003, Vol. 52 Issue 5, p735
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate rnucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated. Methods: LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored. Results: In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression. Conclusions: Expression of the cathelicidin LL-37 in colonocytes and cellular differentiation are separately modulated by SCFA via distinct signalling pathways. These data may provide a rationale for dietary modulation of mucosal defence mechanisms.
ACCESSION #
9737032

 

Related Articles

  • Role of Dietary Fiber and Short-Chain Fatty Acids in the Colon. Andoh, Akira; Tsujikawa, Tomoyuki; Fujiyama, Yoshihide // Current Pharmaceutical Design;Feb2003, Vol. 9 Issue 4, p347 

    Luminal nutrition is important for maintenance of gastrointestinal mucosal structure and function. In particular, short chain fatty acids (SCFAs), metabolic products of anaerobic bacterial fermentation of dietary fiber and resistant starch, are particularly important as the preferred respiratory...

  • Absorption and metabolism of octanoate by the rat colon in vivo: concentration dependency and influence of alternative fuels. Jørgensen, J.R.; Fitch, M.D.; Mortensen, P.B.; Fleming, S.E. // Gut;Jul2002, Vol. 51 Issue 1, p76 

    Background: Compared with short and long chain fatty acids, medium chain fatty acids (MCFAs) have been shown to provide the highest colonic absorption of substrate carbon. Moreover, colonic epithelial cells fulfil their basic energy requirements as easily from MCFAs as from short chain fatty...

  • In vitro fermentation characteristics of a mixture of Raftilose and guar gum by human faecal bacteria. Khan, Khalid M.; Edwards, Christine A. // European Journal of Nutrition;Sep2005, Vol. 44 Issue 6, p371 

    Background The therapeutic effects of indigestible carbohydrates in the human colon are well known. Most fermentation studies have examined only single carbohydrates. Considering the idiosyncratic actions of individual carbohydrates and the dose required, it is unlikely that any one carbohydrate...

  • Collagenous Colitis.  // Current Medical Literature: Gastroenterology;2007, Vol. 26 Issue 4, p113 

    The article discusses research being done on collagenous colitis (CC). It references a study by Wildt et al, published in a 2007 issue of the "European Journal of Gastroenterology & Hepatology." Collagenous colitis is a disease characterized by watery diarrhea, normal mucosal appearances at...

  • Role of Lipoxins and Resolvins as Anti-Inflammatory and Proresolving Mediators in Colon Cancer. Janakiram, Naveena B.; Rao, Chinthalapally V. // Current Molecular Medicine;Jun2009, Vol. 9 Issue 5, p565 

    Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids...

  • High Prevalence of Fatty Acid Synthase Expression in Colorectal Cancers in Middle Eastern Patients and Its Potential Role as a Therapeutic Target. Uddin, Shahab; Hussain, Azhar R.; Ahmed, Maqbool; Abubaker, Jehad; Al-Sanea, Nasser; AbdulJabbar, Alaa; Ashari, Luai H.; Alhomoud, Samar; Al-Dayel, Fouad; Bavi, Prashant; Al-Kuraya, Khawla S. // American Journal of Gastroenterology;Jul2009, Vol. 104 Issue 7, p1790 

    OBJECTIVES:Many human epithelial cancers, particularly those with a poor prognosis, express high levels of fatty acid synthase (FASN), a key metabolic enzyme linked to synthesis of membrane phospholipids in cancer cells. Overexpression of FASN is linked with activation of the...

  • BUTYRATE AND COLONOCYTES: BAX TO THE FRONT. Stollman, Neil H.; Rogers, Arvey I.; Johnson, David // American Journal of Gastroenterology;Sep1997, Vol. 92 Issue 9, p1573 

    Comments on a study on the association of the absence of the fatty acid butyrate with the induction of bux proteins and apoptosis in the proximal colon of guinea pig. Impact of the removal of the fatty acid on colonic mucous; Effect of the shortage of butyrate on colonic inflammation in...

  • THE LINK BETWEEN COLON FERMENTATION AND SYSTEMIC DISEASE. Jenkins, David J. A. // American Journal of Gastroenterology;Nov1989, Vol. 84 Issue 11, p1362 

    Discusses the link between colon fermentation and systemic disease. Information on the colon as a repository for carbohydrate; Specific effects of carbohydrate fermentation; General effects of short chain fatty acids.

  • Enteral and intraluminal short-chain fatty acids improves ischemic left colonic anastomotic healing in the rat. Topçu, Ömer; Karadayi, Kürsat; Kuzu, M. Ayhan; Ulukent, Suat; Erkek, Bülent; Alaçayir, Iskender // International Journal of Colorectal Disease;May2002, Vol. 17 Issue 3, p171 

    Background and aims: This study assessed the effect of short-chain fatty acids (SCFAs) on the healing of ischemic colonic anastomosis and compared the enteral and intraluminal (transrectal) forms of SCFAs in the same study. Material and methods: Left colonic ischemia was induced and a 1-cm left...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics