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Antifungal Treatments Delineate a Correlation between Cathepsins and Cytokines in Murine Model of Invasive Aspergillosis.

Mittal A, Gahlaut A, Sharma GL, Dabur R - Indian J Pharm Sci (2013)

Bottom Line: In the present murine model of invasive pulmonary aspergillosis, on seventh day of Aspergillus fumigatus infection, both kidney and liver showed significant (P<0.05) fungal burdens, which was also confirmed by histological analyses.The data illustrate that the reduction in fungal load in both organs probably results in a decreased local inflammatory response, as measured by decreased levels of interleukin-4 and interleukin-10 and increased level of interferon gamma in the antifungal compounds treated mice.Interestingly, this altered level of cytokines relates well with the activity level of cathepsins, that is decreased in interleukines (interleukinL-4/interleukin-10) and cathepsins (cathepsin B, cathepsin C and cathepsin L); and increase in interferon gamma and cathepsin H levels in the mice treated with antifungal compounds were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University College, Kurukshetra University, Kurukshetra-136 119, India.

ABSTRACT
In the pathogenesis of invasive pulmonary aspergillosis both fungal and host factors play roles. Though cytokines and phagocyte, as host factors, have been shown to participate in defence against Aspergillus species yet the role of cysteine proteases, that is cathepsins, a lysosomal enzymes of phagocytes, remains unknown in fungal infection. Studies are available which shows that cytokines regulate the cysteine proteases processed immune molecules for their further action but their relationship with each other under fungal infection is not clear. Therefore, in this study, we demonstrate the substantial role of cathepsins and cytokines in aspergillosis. In the present murine model of invasive pulmonary aspergillosis, on seventh day of Aspergillus fumigatus infection, both kidney and liver showed significant (P<0.05) fungal burdens, which was also confirmed by histological analyses. The activity profiles of four cathepsins in the kidney and liver tissue were analysed and correlated with blood cytokines level in the presence and absence of antifungal compounds (amphotericin B, a standard drug and 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, isolated in our laboratory from natural source) treatment. The data illustrate that the reduction in fungal load in both organs probably results in a decreased local inflammatory response, as measured by decreased levels of interleukin-4 and interleukin-10 and increased level of interferon gamma in the antifungal compounds treated mice. Interestingly, this altered level of cytokines relates well with the activity level of cathepsins, that is decreased in interleukines (interleukinL-4/interleukin-10) and cathepsins (cathepsin B, cathepsin C and cathepsin L); and increase in interferon gamma and cathepsin H levels in the mice treated with antifungal compounds were observed. These observations support not only the negative (cathepsin B, cathepsin C and cathepsin L) and positive (cathepsin H) role of cathepsins in aspergillosis but also prove the role of cytokines in remodelling of immune response. Overall, the study reveals a correlation between cathepsins and cytokines and their regulatory role in fungal mediated infection.

No MeSH data available.


Related in: MedlinePlus

Expression levels of cytokinins and IgE.Expression levels of (a) interferon-γ (b) interleukin-4 (c) interleukin-10 and (d) IgE in the serum of various groups of animals. *P<0.05 (compared with control mice group, Group-I); #P<0.05, values significantly different from infected groups (Group II and III) of mice.
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Figure 6: Expression levels of cytokinins and IgE.Expression levels of (a) interferon-γ (b) interleukin-4 (c) interleukin-10 and (d) IgE in the serum of various groups of animals. *P<0.05 (compared with control mice group, Group-I); #P<0.05, values significantly different from infected groups (Group II and III) of mice.

Mentions: Cytokines specifically IL-4, IL-10 and IFN-γ are well reported to be involved in fungal mediated infections and play the essential role in immune-functional differentiation. To see the effect of A. fumigatus on these cytokines levels in IPA model, profiles of these cytokines in all five groups were analysed. As seen in fig. 6a and c, the serum levels for IL-4/ IL-10 decreased (~2 fold) while level found high for IFN-γ in the animals treated with antifungal compounds (Group IV and V) compared with infected mice groups (Group II and III). As evident through a published report[30] the level of IgE gets regulated by IL-4/IL-10, therefore the study was also carried out for IgE in all experimental groups. As per fig. 6d, the level of this antibody is found similar to the level of IL-4 and IL-10 in all groups of mice, that is its level increased in infected groups and decreased after treatment.


Antifungal Treatments Delineate a Correlation between Cathepsins and Cytokines in Murine Model of Invasive Aspergillosis.

Mittal A, Gahlaut A, Sharma GL, Dabur R - Indian J Pharm Sci (2013)

Expression levels of cytokinins and IgE.Expression levels of (a) interferon-γ (b) interleukin-4 (c) interleukin-10 and (d) IgE in the serum of various groups of animals. *P<0.05 (compared with control mice group, Group-I); #P<0.05, values significantly different from infected groups (Group II and III) of mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928733&req=5

Figure 6: Expression levels of cytokinins and IgE.Expression levels of (a) interferon-γ (b) interleukin-4 (c) interleukin-10 and (d) IgE in the serum of various groups of animals. *P<0.05 (compared with control mice group, Group-I); #P<0.05, values significantly different from infected groups (Group II and III) of mice.
Mentions: Cytokines specifically IL-4, IL-10 and IFN-γ are well reported to be involved in fungal mediated infections and play the essential role in immune-functional differentiation. To see the effect of A. fumigatus on these cytokines levels in IPA model, profiles of these cytokines in all five groups were analysed. As seen in fig. 6a and c, the serum levels for IL-4/ IL-10 decreased (~2 fold) while level found high for IFN-γ in the animals treated with antifungal compounds (Group IV and V) compared with infected mice groups (Group II and III). As evident through a published report[30] the level of IgE gets regulated by IL-4/IL-10, therefore the study was also carried out for IgE in all experimental groups. As per fig. 6d, the level of this antibody is found similar to the level of IL-4 and IL-10 in all groups of mice, that is its level increased in infected groups and decreased after treatment.

Bottom Line: In the present murine model of invasive pulmonary aspergillosis, on seventh day of Aspergillus fumigatus infection, both kidney and liver showed significant (P<0.05) fungal burdens, which was also confirmed by histological analyses.The data illustrate that the reduction in fungal load in both organs probably results in a decreased local inflammatory response, as measured by decreased levels of interleukin-4 and interleukin-10 and increased level of interferon gamma in the antifungal compounds treated mice.Interestingly, this altered level of cytokines relates well with the activity level of cathepsins, that is decreased in interleukines (interleukinL-4/interleukin-10) and cathepsins (cathepsin B, cathepsin C and cathepsin L); and increase in interferon gamma and cathepsin H levels in the mice treated with antifungal compounds were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University College, Kurukshetra University, Kurukshetra-136 119, India.

ABSTRACT
In the pathogenesis of invasive pulmonary aspergillosis both fungal and host factors play roles. Though cytokines and phagocyte, as host factors, have been shown to participate in defence against Aspergillus species yet the role of cysteine proteases, that is cathepsins, a lysosomal enzymes of phagocytes, remains unknown in fungal infection. Studies are available which shows that cytokines regulate the cysteine proteases processed immune molecules for their further action but their relationship with each other under fungal infection is not clear. Therefore, in this study, we demonstrate the substantial role of cathepsins and cytokines in aspergillosis. In the present murine model of invasive pulmonary aspergillosis, on seventh day of Aspergillus fumigatus infection, both kidney and liver showed significant (P<0.05) fungal burdens, which was also confirmed by histological analyses. The activity profiles of four cathepsins in the kidney and liver tissue were analysed and correlated with blood cytokines level in the presence and absence of antifungal compounds (amphotericin B, a standard drug and 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, isolated in our laboratory from natural source) treatment. The data illustrate that the reduction in fungal load in both organs probably results in a decreased local inflammatory response, as measured by decreased levels of interleukin-4 and interleukin-10 and increased level of interferon gamma in the antifungal compounds treated mice. Interestingly, this altered level of cytokines relates well with the activity level of cathepsins, that is decreased in interleukines (interleukinL-4/interleukin-10) and cathepsins (cathepsin B, cathepsin C and cathepsin L); and increase in interferon gamma and cathepsin H levels in the mice treated with antifungal compounds were observed. These observations support not only the negative (cathepsin B, cathepsin C and cathepsin L) and positive (cathepsin H) role of cathepsins in aspergillosis but also prove the role of cytokines in remodelling of immune response. Overall, the study reveals a correlation between cathepsins and cytokines and their regulatory role in fungal mediated infection.

No MeSH data available.


Related in: MedlinePlus