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The Role of CHI3L1 (Chitinase-3-Like-1) in the Pathogenesis of Infections in Burns in a Mouse Model.

Bohr S, Patel SJ, Vasko R, Shen K, Golberg A, Berthiaume F, Yarmush ML - PLoS ONE (2015)

Bottom Line: Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection.In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor.We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

View Article: PubMed Central - PubMed

Affiliation: Center for Engineering in Medicine, Shriners Hospitals for Children and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Department Plastic and Hand Surgery-Burn Center, UKA University Clinics RWTH, Aachen, Germany.

ABSTRACT
In severe burn injury the unique setting of a depleted, dysfunctional immune system along with a loss of barrier function commonly results in opportunistic infections that eventually proof fatal. Unfortunately, the dynamic sequence of bacterial contamination, colonization and eventually septic invasion with bacteria such as Pseudomonas species is still poorly understood although a limiting factor in clinical decision making. Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection. In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor. We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

No MeSH data available.


Related in: MedlinePlus

CHI3L1, CHIA and CHIT show distinct, organ-specific expression levels in wild type (WT) mice.(A) Intra-organ comparison regarding skin, spleen, lungs, liver or colon demonstrates pre-dominance of CHI3L1 expression levels over CHIA and CHIT. (B) Inter-organ comparison of CHI3L1, CHIA or CHIT each also reveals an apparent biological relevance e.g. of CHI3L1-expression in lung tissue (qPCR /ΔΔCt-method: n≥4; normalized to lowest expression value of each data set = fold change).
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pone.0140440.g001: CHI3L1, CHIA and CHIT show distinct, organ-specific expression levels in wild type (WT) mice.(A) Intra-organ comparison regarding skin, spleen, lungs, liver or colon demonstrates pre-dominance of CHI3L1 expression levels over CHIA and CHIT. (B) Inter-organ comparison of CHI3L1, CHIA or CHIT each also reveals an apparent biological relevance e.g. of CHI3L1-expression in lung tissue (qPCR /ΔΔCt-method: n≥4; normalized to lowest expression value of each data set = fold change).

Mentions: First, we evaluated the organ-specific expression of the three main chitinases found in mammals including humans and WT mice using RT-qPCR: CHI3L1, CHIA and CHIT. Here we distinguished between intra- and inter-organ analysis referring to comparative expression between different chitinases within one organ as well as organ-specific expression levels for each chitinase. The main finding was that CHI3L1 appears to be the predominantly expressed chitinase in mice with ~100–1000 fold higher expression levels compared to CHIA and CHIT in an intra-organ comparison. CHIT1 appeared to be predominently expressed in colon and skin tissue whereas CHIA expression was low in all investigated organs compared to CHI3L1 and CHIA (Fig 1A). Also, with inter-organ analysis, CHI3L1 showed highest constitutive expression levels in lung tissue and lowest in colon conditions. CHIT showed highest expression in lung, skin or colon and lowest in spleen and liver. Again, CHIA showed highest expression levels in lung and lowest in Liver (Fig 1B).


The Role of CHI3L1 (Chitinase-3-Like-1) in the Pathogenesis of Infections in Burns in a Mouse Model.

Bohr S, Patel SJ, Vasko R, Shen K, Golberg A, Berthiaume F, Yarmush ML - PLoS ONE (2015)

CHI3L1, CHIA and CHIT show distinct, organ-specific expression levels in wild type (WT) mice.(A) Intra-organ comparison regarding skin, spleen, lungs, liver or colon demonstrates pre-dominance of CHI3L1 expression levels over CHIA and CHIT. (B) Inter-organ comparison of CHI3L1, CHIA or CHIT each also reveals an apparent biological relevance e.g. of CHI3L1-expression in lung tissue (qPCR /ΔΔCt-method: n≥4; normalized to lowest expression value of each data set = fold change).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631332&req=5

pone.0140440.g001: CHI3L1, CHIA and CHIT show distinct, organ-specific expression levels in wild type (WT) mice.(A) Intra-organ comparison regarding skin, spleen, lungs, liver or colon demonstrates pre-dominance of CHI3L1 expression levels over CHIA and CHIT. (B) Inter-organ comparison of CHI3L1, CHIA or CHIT each also reveals an apparent biological relevance e.g. of CHI3L1-expression in lung tissue (qPCR /ΔΔCt-method: n≥4; normalized to lowest expression value of each data set = fold change).
Mentions: First, we evaluated the organ-specific expression of the three main chitinases found in mammals including humans and WT mice using RT-qPCR: CHI3L1, CHIA and CHIT. Here we distinguished between intra- and inter-organ analysis referring to comparative expression between different chitinases within one organ as well as organ-specific expression levels for each chitinase. The main finding was that CHI3L1 appears to be the predominantly expressed chitinase in mice with ~100–1000 fold higher expression levels compared to CHIA and CHIT in an intra-organ comparison. CHIT1 appeared to be predominently expressed in colon and skin tissue whereas CHIA expression was low in all investigated organs compared to CHI3L1 and CHIA (Fig 1A). Also, with inter-organ analysis, CHI3L1 showed highest constitutive expression levels in lung tissue and lowest in colon conditions. CHIT showed highest expression in lung, skin or colon and lowest in spleen and liver. Again, CHIA showed highest expression levels in lung and lowest in Liver (Fig 1B).

Bottom Line: Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection.In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor.We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

View Article: PubMed Central - PubMed

Affiliation: Center for Engineering in Medicine, Shriners Hospitals for Children and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Department Plastic and Hand Surgery-Burn Center, UKA University Clinics RWTH, Aachen, Germany.

ABSTRACT
In severe burn injury the unique setting of a depleted, dysfunctional immune system along with a loss of barrier function commonly results in opportunistic infections that eventually proof fatal. Unfortunately, the dynamic sequence of bacterial contamination, colonization and eventually septic invasion with bacteria such as Pseudomonas species is still poorly understood although a limiting factor in clinical decision making. Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection. In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor. We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

No MeSH data available.


Related in: MedlinePlus