Abstracts (complete list) - Wissenschaft Online

Nadine Nippe, Katja Gutsche, Mechthild Jung, Gerald Grütz
Immunoregulation of IL-10 induced Autotaxin
Cytokines are regulators of host response to inflammation. Some cytokines have to be
associated with the pathogenesis of diseases, whereas others serve to reduce
inflammatory responses. The mediator of inflammation HMGB1 and IL-1ß are secreted
by monocytes and macrophages through a non-classical pathway.
High-mobility group protein 1(HMGB1), a non-histone nuclear protein, functions as a
late mediator of inflammation. Passive immunization with anti-HMGB1 antibodies
protects against endotoxin lethality in mice. Active secretion of HMGB1 by monocytes
and macrophages occurs in response to LPS. We show that its release can also be
triggered by LPC.
Secretion of IL-1ß needs two distinct stimuli. An initial inflammatory stimulus, LPS,
induces synthesis of pro-IL-1ß, processing and release of matured IL-1ß is inefficient. A
secondary stimulus such as ATP can trigger rapid processing and massive release of IL-
1ß.
IL-10 is one of the major immunosuppressive cytokine. It strongly down-regulates the
expression of proinflammatory cytokines. In order to identify genes which could mediate
the IL-10 inhibition we analyzed the expression profile of IL-10 regulated genes in
human monocytes by comparison of expression level of 12000 genes in IL-10
stimulated monocytes and unstimulated cells. A possible candidate is Autotaxin. We
show that Autotaxin is highly up regulated by IL-10 in human monocytes.
Autotaxin is an ecto-enzyme with pyrophosphatase/phosphodiesterase-activity. But
primarily functions as a lysophospholipase D, degrading lysophosphatidylcholine (LPC)
into lysophosphatidic acid (LPA).
Therefore, we hypothesized that Autotaxin could reduces HMGB1 and IL-1ß release by
degradation of LPC and ATP. We would like to demonstrate first functional results.