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[Immunology] Re: Osteopontin and Fibrosis

John H. j_hasenkam at yahoo.com.au
Tue Sep 12 17:38:23 EST 2006


Thanks Bryan,

I've used pubmed and a variety of other databases, my interest in
osteopontin was prompted by a recent microarray analysis showing it is
highly elevated in IPF, but of course which comes first: ipf or
osteopontin??? It certainly appears to be a case of unresolved healing,
which often can induce an inflammatory cascade, though the studies
indicate that gc administration has no value. TGF beta is a good target
as it seems to encourage fibroblast migration and I'm currently trying
to figure out the relationship between tgf beta, smad 3 and 7, and
vitamin D receptor. Vitamin D does have a facilitative effect upon tgf
beta and is also found to be important in maintaining lung health, only
in cases of ipf one wonders if perhaps tgf beta should be inhibited.
Yet ipf appears to be Th 1 mediated inflammation and vitamin D and tfg
beta tend to skew the response to a th 2 type, so I'm thoroughly
confused ... . I suspect the inflammatory aspect is secondary. Known
risk factors are: dusty environments, smoking, and strangely enough in
one study the highest risk group was hairdressers(all those airborne
chemicals ... ). So yes causative factors are many and varied, the
commonality being lung irritation. What would be interesting to know is
if the rates of ipf correlate with air pollution and are slowly
increasing.

I'm quite naive about all this so I appreciate your input.


Regards,


John.



Bryan Heit wrote:
> John H. wrote:
> > Lately I've been doing some digging around in relation to idiopathic
> > pulmonary fibrosis and chronic heart failure. To my surprise
> > osteopontin is upregulated in both cases and is now being perceived as
> > a primary driver of fibrosis. It is known that aldosterone increases
> > osteopontin production (MR specific antagonists are very efficacious in
> > chronic heart failure) but I'm looking for other possible causes of
> > increased osteopontin production because it is doubtful that it is the
> > causative factor in relation to idiopathic pulmonary fibrosis. Possible
> > targets are:
> >
> > tgf beta
> > il-1
> > tnfa
> > Smad 3 or 7???
> >
> > Can anyone here help me?
> >
> >
> > John.
>
> Your best bet is pubmed.gov - this page will let you search the medical
> literature for pretty much any information you want.  In terms of
> idiopathic lung fibrosis, several potential causative agents have been
> identified.  Included in that list is osteopontin, TGF-b, TNF, IL-8,
> IGF-1, leukotrienes, and a whole slew of other mediators.  As for the
> causative agent, that is unknown (hence the idiopathic).  By and large,
> it is considered to be a failure of the body to stop the wound healing
> process after some form of inflammatory damage to the lungs.  Why this
> occurs (and why it doesn't occur in the majority of people who
> experience lung inflammation) is a mystery.
>
> Some proposed causative agents include persistent viral infections,
> unresolved or chronic inflammation, increased oxidative stress within
> the lung, genetics, and autoimmunity.  This broad spectrum of potential
> causative agents has led some people to propose that IPF may actually be
> a collection of diseases, rather then one disease, which just happen to
> share common symptoms.
>
> Some reviews:
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12475802&query_hl=1&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16500642&query_hl=4&itool=pubmed_docsum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16262559&query_hl=4&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16214821&query_hl=4&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16093819&query_hl=4&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15894605&query_hl=4&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15863652&query_hl=4&itool=pubmed_DocSum
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15648777&query_hl=4&itool=pubmed_DocSum
> 
> Bryan



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